{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T23:23:53Z","timestamp":1772148233535,"version":"3.50.1"},"reference-count":81,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2021,11,27]],"date-time":"2021-11-27T00:00:00Z","timestamp":1637971200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,27]],"date-time":"2021-11-27T00:00:00Z","timestamp":1637971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Czech Science Foundation project","award":["No. 19-05048S"],"award-info":[{"award-number":["No. 19-05048S"]}]},{"name":"Operational Programme \u201cResearch, Development and Education\u201d","award":["project CZ.02.1.01\/0.0\/0.0\/16_019\/0000785 \"Centre for Tumour Ecology-Research of the Cancer Microenvironment Supporting Cancer Growth Spread\""],"award-info":[{"award-number":["project CZ.02.1.01\/0.0\/0.0\/16_019\/0000785 \"Centre for Tumour Ecology-Research of the Cancer Microenvironment Supporting Cancer Growth Spread\""]}]},{"DOI":"10.13039\/100007397","name":"Univerzita Karlova v Praze","doi-asserted-by":"publisher","award":["PROGRESS Q28"],"award-info":[{"award-number":["PROGRESS Q28"]}],"id":[{"id":"10.13039\/100007397","id-type":"DOI","asserted-by":"publisher"}]},{"name":"League Against Cancer Prague grant"},{"DOI":"10.13039\/501100008530","name":"ERDF","doi-asserted-by":"crossref","award":["CZ.02.1.01\/0.0\/0.0\/16_013\/0001775"],"award-info":[{"award-number":["CZ.02.1.01\/0.0\/0.0\/16_013\/0001775"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008530","name":"ERDF","doi-asserted-by":"crossref","award":["CZ.02.1.01\/0.0\/0.0\/18_046\/0016045"],"award-info":[{"award-number":["CZ.02.1.01\/0.0\/0.0\/18_046\/0016045"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]},{"name":"MEYS","award":["LM2018129"],"award-info":[{"award-number":["LM2018129"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Histochem Cell Biol"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The incidence of cutaneous malignant melanoma is increasing worldwide. While the treatment of initial stages of the disease is simple, the advanced disease frequently remains fatal despite novel therapeutic options . This requires identification of novel therapeutic targets in melanoma. Similarly to other types of tumours, the cancer microenvironment plays a prominent role and determines the biological properties of melanoma. Importantly, melanoma cell-produced exosomes represent an important tool of intercellular communication within this cancer ecosystem. We have focused on potential differences in the activity of exosomes produced by melanoma cells towards melanoma-associated fibroblasts and normal dermal fibroblasts. Cancer-associated fibroblasts were activated by the melanoma cell-produced exosomes significantly more than their normal counterparts, as assessed by increased transcription of genes for inflammation-supporting cytokines and chemokines, namely IL-6 or IL-8. We have observed that the response is dependent on the duration of the stimulus via exosomes and also on the quantity of exosomes. Our study demonstrates that melanoma-produced exosomes significantly stimulate the tumour-promoting proinflammatory activity of cancer-associated fibroblasts. This may represent a potential new target of oncologic therapy .<\/jats:p>","DOI":"10.1007\/s00418-021-02052-2","type":"journal-article","created":{"date-parts":[[2021,11,27]],"date-time":"2021-11-27T11:02:42Z","timestamp":1638010962000},"page":"153-172","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Exosomes produced by melanoma cells significantly influence the biological properties of normal and cancer-associated fibroblasts"],"prefix":"10.1007","volume":"157","author":[{"given":"Karol\u00edna","family":"Strnadov\u00e1","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucie","family":"Pfeiferov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petr","family":"P\u0159ikryl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbora","family":"Dvo\u0159\u00e1nkov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik","family":"Vl\u010d\u00e1k","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana","family":"Fr\u00fddlov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Vokurka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji\u0159\u00ed","family":"Novotn\u00fd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana","family":"\u0160\u00e1chov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milu\u0161e","family":"Hradilov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Br\u00e1bek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana","family":"\u0160migov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"R\u00f6sel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Karel","family":"Smetana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal","family":"Kol\u00e1\u0159","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1750-9933","authenticated-orcid":false,"given":"Luk\u00e1\u0161","family":"Lacina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,11,27]]},"reference":[{"key":"2052_CR1","unstructured":"Alberts B, Johnson A, Lewis J, et al (2002) Cancer as a Microevolutionary Process. Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK26891\/. Accessed 01 June 2021"},{"key":"2052_CR2","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/75556","volume":"25","author":"M Ashburner","year":"2000","unstructured":"Ashburner M, Ball CA, Blake JA et al (2000) Gene ontology: tool for the unification of biology. Nat Genet 25:25\u201329","journal-title":"Nat Genet"},{"key":"2052_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms21217937","volume":"21","author":"J Br\u00e1bek","year":"2020","unstructured":"Br\u00e1bek J, Jakubek M, Vellieux F et al (2020) Interleukin-6: molecule in the intersection of cancer, ageing and COVID-19. Int J Mol Sci 21:1\u201325","journal-title":"Int J Mol Sci"},{"key":"2052_CR4","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-57497-7","author":"K Brennan","year":"2020","unstructured":"Brennan K, Martin K, FitzGerald SP et al (2020) A comparison of methods for the isolation and separation of extracellular vesicles from protein and lipid particles in human serum. Sci Rep. https:\/\/doi.org\/10.1038\/s41598-020-57497-7","journal-title":"Sci Rep"},{"key":"2052_CR5","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1038\/bjc.2014.364","volume":"111","author":"OT Brustugun","year":"2014","unstructured":"Brustugun OT, M\u00f8ller B, Helland \u00c5 (2014) Years of life lost as a measure of cancer burden on a national level. Br J Cancer 111:1014\u20131020. https:\/\/doi.org\/10.1038\/bjc.2014.364","journal-title":"Br J Cancer"},{"key":"2052_CR6","doi-asserted-by":"publisher","first-page":"3468","DOI":"10.1111\/cas.14578","volume":"111","author":"L Bu","year":"2020","unstructured":"Bu L, Baba H, Yasuda T et al (2020) Functional diversity of cancer-associated fibroblasts in modulating drug resistance. Cancer Sci 111:3468\u20133477. https:\/\/doi.org\/10.1111\/cas.14578","journal-title":"Cancer Sci"},{"key":"2052_CR7","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1007\/s00281-018-0682-0","volume":"40","author":"EI Buz\u00e1s","year":"2018","unstructured":"Buz\u00e1s EI, T\u00f3th E, S\u00f3dar BW, Szab\u00f3-Taylor K (2018) Molecular interactions at the surface of extracellular vesicles. Semin Immunopathol 40:453\u2013464","journal-title":"Semin Immunopathol"},{"key":"2052_CR8","doi-asserted-by":"publisher","first-page":"9739","DOI":"10.3390\/ijms21249739","volume":"21","author":"GA Cabral-Pacheco","year":"2020","unstructured":"Cabral-Pacheco GA, Garza-Veloz I, Castruita-De la Rosa C et al (2020) The roles of matrix metalloproteinases and their inhibitors in human diseases. Int J Mol Sci 21:9739. https:\/\/doi.org\/10.3390\/ijms21249739","journal-title":"Int J Mol Sci"},{"key":"2052_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms21186768","volume":"21","author":"C Cavallari","year":"2020","unstructured":"Cavallari C, Camussi G, Brizzi MF (2020) Extracellular vesicles in the tumour microenvironment: eclectic supervisors. Int J Mol Sci 21:1\u201321","journal-title":"Int J Mol Sci"},{"key":"2052_CR10","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1152\/physiol.00036.2016","volume":"32","author":"K Duval","year":"2017","unstructured":"Duval K, Grover H, Han LH et al (2017) Modeling physiological events in 2D vs. 3D cell culture. Physiology 32:266\u2013277","journal-title":"Physiology"},{"key":"2052_CR11","first-page":"393","volume-title":"Skin stem cells: methods and protocols","author":"B Dvo\u0159\u00e1nkov\u00e1","year":"2019","unstructured":"Dvo\u0159\u00e1nkov\u00e1 B, Lacina L, Smetana K (2019) Isolation of normal fibroblasts and their cancer-associated counterparts (CAFs) for biomedical research. In: Turksen K (ed) Skin stem cells: methods and protocols. Springer, New York, pp 393\u2013406"},{"key":"2052_CR12","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1016\/j.devcel.2010.05.012","volume":"18","author":"M Egeblad","year":"2010","unstructured":"Egeblad M, Nakasone ES, Werb Z (2010) Tumors as organs: complex tissues that interface with the entire organism. Dev Cell 18:884\u2013901","journal-title":"Dev Cell"},{"key":"2052_CR13","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1002\/ehf2.12509","volume":"6","author":"L Emelyanova","year":"2019","unstructured":"Emelyanova L, Sra A, Schmuck EG et al (2019) Impact of statins on cellular respiration and de-differentiation of myofibroblasts in human failing hearts. ESC Heart Fail 6:1027\u20131040. https:\/\/doi.org\/10.1002\/ehf2.12509","journal-title":"ESC Heart Fail"},{"key":"2052_CR14","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1038\/s41587-020-0439-x","volume":"38","author":"PA Ewels","year":"2020","unstructured":"Ewels PA, Peltzer A, Fillinger S et al (2020) The nf-core framework for community-curated bioinformatics pipelines. Nat Biotechnol 38:276\u2013278. https:\/\/doi.org\/10.1038\/s41587-020-0439-x","journal-title":"Nat Biotechnol"},{"key":"2052_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/cancers12102870","volume":"12","author":"I Falcone","year":"2020","unstructured":"Falcone I, Conciatori F, Bazzichetto C et al (2020) Tumor microenvironment: Implications in melanoma resistance to targeted therapy and immunotherapy. Cancers 12:1\u201326","journal-title":"Cancers"},{"key":"2052_CR16","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-019-0994-2","author":"ME Fiori","year":"2019","unstructured":"Fiori ME, di Franco S, Villanova L et al (2019) Cancer-associated fibroblasts as abettors of tumor progression at the crossroads of EMT and therapy resistance. Mol Cancer. https:\/\/doi.org\/10.1186\/s12943-019-0994-2","journal-title":"Mol Cancer"},{"key":"2052_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1658","author":"C Gaggioli","year":"2007","unstructured":"Gaggioli C, Hooper S, Hidalgo-Carcedo C et al (2007) Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. Nat Cell Biol. https:\/\/doi.org\/10.1038\/ncb1658","journal-title":"Nat Cell Biol"},{"key":"2052_CR18","doi-asserted-by":"publisher","first-page":"2521","DOI":"10.1002\/ijc.32521","volume":"145","author":"T Gener Lahav","year":"2019","unstructured":"Gener Lahav T, Adler O, Zait Y et al (2019) Melanoma-derived extracellular vesicles instigate proinflammatory signaling in the metastatic microenvironment. Int J Cancer 145:2521\u20132534. https:\/\/doi.org\/10.1002\/ijc.32521","journal-title":"Int J Cancer"},{"key":"2052_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-019-39553-z","volume":"9","author":"B Gok Yavuz","year":"2019","unstructured":"Gok Yavuz B, Gunaydin G, Gedik ME et al (2019) Cancer associated fibroblasts sculpt tumour microenvironment by recruiting monocytes and inducing immunosuppressive PD-1 + TAMs. Sci Rep 9:1\u201315. https:\/\/doi.org\/10.1038\/s41598-019-39553-z","journal-title":"Sci Rep"},{"key":"2052_CR20","doi-asserted-by":"publisher","first-page":"2828","DOI":"10.2174\/1381612825666190716102037","volume":"25","author":"B Gorain","year":"2019","unstructured":"Gorain B, Choudhury H, Yee GS, Bhattamisra SK (2019) Adenosine receptors as novel targets for the treatment of various cancers. Curr Pharm Des 25:2828\u20132841. https:\/\/doi.org\/10.2174\/1381612825666190716102037","journal-title":"Curr Pharm Des"},{"key":"2052_CR21","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/jid.2012.263","volume":"133","author":"J Grahovac","year":"2013","unstructured":"Grahovac J, Becker D, Wells A (2013) Melanoma cell invasiveness is promoted at least in part by the epidermal growth factor-like repeats of tenascin-C. J Invest Dermatol 133:210\u2013220. https:\/\/doi.org\/10.1038\/jid.2012.263","journal-title":"J Invest Dermatol"},{"key":"2052_CR22","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","volume":"32","author":"Z Gu","year":"2016","unstructured":"Gu Z, Eils R, Schlesner M (2016) Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics 32:2847\u20132849. https:\/\/doi.org\/10.1093\/bioinformatics\/btw313","journal-title":"Bioinformatics"},{"key":"2052_CR23","doi-asserted-by":"publisher","DOI":"10.21769\/bioprotoc.2646","author":"H Hamidi","year":"2017","unstructured":"Hamidi H, Lilja J, Ivaska J (2017) Using xCELLigence RTCA instrument to measure cell adhesion. Bio-Protocol. https:\/\/doi.org\/10.21769\/bioprotoc.2646","journal-title":"Bio-Protocol"},{"key":"2052_CR24","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1016\/S0002-9440(10)65023-7","volume":"156","author":"M-Y Hsu","year":"2000","unstructured":"Hsu M-Y, Meier FE, Nesbit M et al (2000) E-cadherin expression in melanoma cells restores keratinocyte-mediated growth control and down-regulates expression of invasion-related adhesion receptors. Am J Pathol 156:1515\u20131525. https:\/\/doi.org\/10.1016\/S0002-9440(10)65023-7","journal-title":"Am J Pathol"},{"key":"2052_CR25","doi-asserted-by":"publisher","first-page":"3085","DOI":"10.1080\/15384101.2019.1669380","volume":"18","author":"T Hu","year":"2019","unstructured":"Hu T, Hu J (2019) Melanoma-derived exosomes induce reprogramming fibroblasts into cancer-associated fibroblasts via Gm26809 delivery. Cell Cycle 18:3085\u20133094. https:\/\/doi.org\/10.1080\/15384101.2019.1669380","journal-title":"Cell Cycle"},{"key":"2052_CR26","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1111\/fcp.12495","volume":"34","author":"L Ji","year":"2020","unstructured":"Ji L, Liu C, Yuan Y et al (2020) Key roles of Rho GTPases, YAP, and Mutant P53 in anti-neoplastic effects of statins. Fundam Clin Pharmacol 34:4\u201310. https:\/\/doi.org\/10.1111\/fcp.12495","journal-title":"Fundam Clin Pharmacol"},{"key":"2052_CR27","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-016-1433-8","author":"NP Jobe","year":"2016","unstructured":"Jobe NP, R\u00f6sel D, Dvo\u0159\u00e1nkov\u00e1 B et al (2016) Simultaneous blocking of IL-6 and IL-8 is sufficient to fully inhibit CAF-induced human melanoma cell invasiveness. Histochem Cell Biol. https:\/\/doi.org\/10.1007\/s00418-016-1433-8","journal-title":"Histochem Cell Biol"},{"key":"2052_CR28","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-018-1650-4","author":"NP Jobe","year":"2018","unstructured":"Jobe NP, \u017divicov\u00e1 V, Mifkov\u00e1 A et al (2018) Fibroblasts potentiate melanoma cells in vitro invasiveness induced by UV-irradiated keratinocytes. Histochem Cell Biol. https:\/\/doi.org\/10.1007\/s00418-018-1650-4","journal-title":"Histochem Cell Biol"},{"key":"2052_CR29","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.3317","volume":"12","author":"D Kim","year":"2015","unstructured":"Kim D, Langmead B, Salzberg SL (2015) HISAT: a fast spliced aligner with low memory requirements. Nat Methods 12:357\u2013360. https:\/\/doi.org\/10.1038\/nmeth.3317","journal-title":"Nat Methods"},{"key":"2052_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-017-08433-9","volume":"7","author":"HY Kim","year":"2017","unstructured":"Kim HY, Lee H, Kim SH et al (2017) Discovery of potential biomarkers in human melanoma cells with different metastatic potential by metabolic and lipidomic profiling. Sci Rep 7:1\u201314. https:\/\/doi.org\/10.1038\/s41598-017-08433-9","journal-title":"Sci Rep"},{"key":"2052_CR31","doi-asserted-by":"publisher","first-page":"619","DOI":"10.3892\/ijo.2020.5090","volume":"57","author":"O Kodet","year":"2020","unstructured":"Kodet O, Ku\u010dera J, Strnadov\u00e1 K et al (2020) Cutaneous melanoma dissemination is dependent on the malignant cell properties and factors of intercellular crosstalk in the cancer microenvironment (review). Int J Oncol 57:619\u2013630. https:\/\/doi.org\/10.3892\/ijo.2020.5090","journal-title":"Int J Oncol"},{"key":"2052_CR32","doi-asserted-by":"publisher","DOI":"10.3892\/or.2019.7319","author":"J Ku\u010dera","year":"2019","unstructured":"Ku\u010dera J, Strnadov\u00e1 K, Dvo\u0159\u00e1nkov\u00e1 B et al (2019) Serum proteomic analysis of melanoma patients with immunohistochemical profiling of primary melanomas and cultured cells: pilot study. Oncol Rep. https:\/\/doi.org\/10.3892\/or.2019.7319","journal-title":"Oncol Rep"},{"key":"2052_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-31323-7","author":"S la Shu","year":"2018","unstructured":"la Shu S, Yang Y, Allen CL et al (2018) Metabolic reprogramming of stromal fibroblasts by melanoma exosome microRNA favours a pre-metastatic microenvironment. Sci Rep. https:\/\/doi.org\/10.1038\/s41598-018-31323-7","journal-title":"Sci Rep"},{"key":"2052_CR34","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1080\/08820139.2020.1803353","volume":"49","author":"S la Shu","year":"2020","unstructured":"la Shu S, Matsuzaki J, Want MY et al (2020) An immunosuppressive effect of melanoma-derived exosomes on NY-ESO-1 antigen-specific human CD8+ T cells is dependent on IL-10 and independent of BRAFV600E mutation in melanoma cell lines. Immunol Investig 49:744\u2013757. https:\/\/doi.org\/10.1080\/08820139.2020.1803353","journal-title":"Immunol Investig"},{"key":"2052_CR35","doi-asserted-by":"publisher","DOI":"10.3390\/ijms161024094","author":"L Lacina","year":"2015","unstructured":"Lacina L, Plzak J, Kodet O et al (2015) Cancer microenvironment: what can we learn from the stem cell niche. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms161024094","journal-title":"Int J Mol Sci"},{"key":"2052_CR36","doi-asserted-by":"publisher","DOI":"10.14670\/HH-18-033","author":"L Lacina","year":"2019","unstructured":"Lacina L, Br\u00e1bek J, Kr\u00e1l V et al (2019) Interleukin-6: a molecule with complex biological impact in cancer. Histol Histopathol. https:\/\/doi.org\/10.14670\/HH-18-033","journal-title":"Histol Histopathol"},{"key":"2052_CR37","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1111\/pcmr.12380","volume":"28","author":"I Lazar","year":"2015","unstructured":"Lazar I, Clement E, Ducoux-Petit M et al (2015) Proteome characterization of melanoma exosomes reveals a specific signature for metastatic cell lines. Pigment Cell Melanoma Res 28:464\u2013475. https:\/\/doi.org\/10.1111\/pcmr.12380","journal-title":"Pigment Cell Melanoma Res"},{"key":"2052_CR38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-020-65628-3","volume":"10","author":"AH Lee","year":"2020","unstructured":"Lee AH, Ghosh D, Quach N et al (2020) Ovarian cancer exosomes trigger differential biophysical response in tumor-derived fibroblasts. Sci Rep 10:1\u201316. https:\/\/doi.org\/10.1038\/s41598-020-65628-3","journal-title":"Sci Rep"},{"key":"2052_CR39","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7652-2_7","author":"K Li","year":"2018","unstructured":"Li K, Wong DK, Hong KY, Raffai RL (2018) Cushioned-density gradient ultracentrifugation (C-DGUC): a refined and high performance method for the, isolation, characterization, and use of exosomes. Methods Mol Biol. https:\/\/doi.org\/10.1007\/978-1-4939-7652-2_7","journal-title":"Methods Mol Biol"},{"key":"2052_CR40","doi-asserted-by":"publisher","first-page":"4253","DOI":"10.2147\/CMAR.S254596","volume":"12","author":"J Li","year":"2020","unstructured":"Li J, Gao Y, Yue W (2020) The clinical diagnostic and prognostic value of dickkopf-1 in cancer. Cancer Manag Res 12:4253\u20134260. https:\/\/doi.org\/10.2147\/CMAR.S254596","journal-title":"Cancer Manag Res"},{"key":"2052_CR41","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","volume":"30","author":"Y Liao","year":"2014","unstructured":"Liao Y, Smyth GK, Shi W (2014) featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30:923\u2013930. https:\/\/doi.org\/10.1093\/bioinformatics\/btt656","journal-title":"Bioinformatics"},{"key":"2052_CR42","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-020-00776-9","author":"W Lin","year":"2020","unstructured":"Lin W, Noel P, Borazanci EH et al (2020) Single-cell transcriptome analysis of tumor and stromal compartments of pancreatic ductal adenocarcinoma primary tumors and metastatic lesions. Genome Med. https:\/\/doi.org\/10.1186\/s13073-020-00776-9","journal-title":"Genome Med"},{"key":"2052_CR43","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1016\/j.bbrc.2019.03.136","volume":"512","author":"X Liu","year":"2019","unstructured":"Liu X, Zhu L, Wang R et al (2019) IFN\u03b3 inhibits fibroblast-leading tumor cell invasion through downregulating N-cadherin. Biochem Biophys Res Commun 512:544\u2013551. https:\/\/doi.org\/10.1016\/j.bbrc.2019.03.136","journal-title":"Biochem Biophys Res Commun"},{"key":"2052_CR44","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love MI, Huber W, Anders S (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15:550. https:\/\/doi.org\/10.1186\/s13059-014-0550-8","journal-title":"Genome Biol"},{"key":"2052_CR45","doi-asserted-by":"publisher","DOI":"10.1101\/234872","author":"ATL Lun","year":"2018","unstructured":"Lun ATL, Riesenfeld S, Andrews T et al (2018) Distinguishing cells from empty droplets in droplet-based single-cell RNA sequencing data. bioRxiv. https:\/\/doi.org\/10.1101\/234872","journal-title":"bioRxiv"},{"key":"2052_CR46","doi-asserted-by":"publisher","first-page":"1830","DOI":"10.1093\/bioinformatics\/btt285","volume":"29","author":"W Luo","year":"2013","unstructured":"Luo W, Brouwer C (2013) Pathview: an R\/Bioconductor package for pathway-based data integration and visualization. Bioinformatics 29:1830\u20131831. https:\/\/doi.org\/10.1093\/bioinformatics\/btt285","journal-title":"Bioinformatics"},{"key":"2052_CR47","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20656","author":"E Mart\u00edn-Villar","year":"2005","unstructured":"Mart\u00edn-Villar E, Scholl FG, Gamallo C et al (2005) Characterization of human PA2.26 antigen (T1\u03b1-2, podoplanin), a small membrane mucin induced in oral squamous cell carcinomas. Int J Cancer. https:\/\/doi.org\/10.1002\/ijc.20656","journal-title":"Int J Cancer"},{"key":"2052_CR48","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.matbio.2018.05.002","volume":"78\u201379","author":"CO McAtee","year":"2019","unstructured":"McAtee CO, Booth C, Elowsky C et al (2019) Prostate tumor cell exosomes containing hyaluronidase Hyal1 stimulate prostate stromal cell motility by engagement of FAK-mediated integrin signaling. Matrix Biol 78\u201379:165\u2013179. https:\/\/doi.org\/10.1016\/j.matbio.2018.05.002","journal-title":"Matrix Biol"},{"key":"2052_CR49","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","volume":"65","author":"T Mosmann","year":"1983","unstructured":"Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55\u201363. https:\/\/doi.org\/10.1016\/0022-1759(83)90303-4","journal-title":"J Immunol Methods"},{"key":"2052_CR50","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1111\/exd.13372","volume":"26","author":"H Niessner","year":"2017","unstructured":"Niessner H, Kosnopfel C, Sinnberg T et al (2017) Combined activity of temozolomide and the mTOR inhibitor temsirolimus in metastatic melanoma involves DKK1. Exp Dermatol 26:598\u2013606. https:\/\/doi.org\/10.1111\/exd.13372","journal-title":"Exp Dermatol"},{"key":"2052_CR51","doi-asserted-by":"publisher","DOI":"10.1002\/path.5618","author":"N Nishimichi","year":"2021","unstructured":"Nishimichi N, Tsujino K, Kanno K et al (2021) Induced hepatic stellate cell integrin, \u03b18\u03b21, enhances cellular contractility and TGF\u03b2 activity in liver fibrosis. J Pathol. https:\/\/doi.org\/10.1002\/path.5618","journal-title":"J Pathol"},{"key":"2052_CR52","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/cancers12113324","volume":"12","author":"J Novotn\u00fd","year":"2020","unstructured":"Novotn\u00fd J, Strnadov\u00e1 K, Dvo\u0159\u00e1nkov\u00e1 B et al (2020) Single-cell RNA sequencing unravels heterogeneity of the stromal niche in cutaneous melanoma heterogeneous spheroids. Cancers 12:1\u201322. https:\/\/doi.org\/10.3390\/cancers12113324","journal-title":"Cancers"},{"key":"2052_CR53","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1203\/00006450-197804001-00732","volume":"12","author":"PT Peebles","year":"1978","unstructured":"Peebles PT, Trisch T, Papageorge AG (1978) 727 isolation of four unusual pediatric solid tumor cell lines. Pediatr Res 12:485\u2013485. https:\/\/doi.org\/10.1203\/00006450-197804001-00732","journal-title":"Pediatr Res"},{"key":"2052_CR54","doi-asserted-by":"publisher","first-page":"2012","DOI":"10.3390\/jcm4121957","volume":"4","author":"S Pfeffer","year":"2015","unstructured":"Pfeffer S, Grossmann K, Cassidy P et al (2015) Detection of exosomal miRNAs in the plasma of melanoma patients. J Clin Med 4:2012\u20132027. https:\/\/doi.org\/10.3390\/jcm4121957","journal-title":"J Clin Med"},{"key":"2052_CR55","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11040440","author":"J Plz\u00e1k","year":"2019","unstructured":"Plz\u00e1k J, Bou\u010dek J, Band\u00farov\u00e1 V et al (2019) The head and neck squamous cell carcinoma microenvironment as a potential target for cancer therapy. Cancers. https:\/\/doi.org\/10.3390\/cancers11040440","journal-title":"Cancers"},{"key":"2052_CR56","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s12015-017-9772-y","volume":"14","author":"F Preisner","year":"2018","unstructured":"Preisner F, Leimer U, Sandmann S et al (2018) Impact of human adipose tissue-derived stem cells on malignant melanoma cells in an in vitro co-culture model. Stem Cell Rev 14:125\u2013140. https:\/\/doi.org\/10.1007\/s12015-017-9772-y","journal-title":"Stem Cell Rev"},{"key":"2052_CR57","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1083\/jcb.115.1.191","volume":"115","author":"PHA Quax","year":"1991","unstructured":"Quax PHA, van Muijen GNP, Weening-Verhoeff EJD et al (1991) Metastatic behavior of human melanoma cell lines in nude mice correlates with urokinase-type plasminogen activator, its type-1 inhibitor, and urokinase-mediated matrix degradation. J Cell Biol 115:191\u2013199. https:\/\/doi.org\/10.1083\/jcb.115.1.191","journal-title":"J Cell Biol"},{"key":"2052_CR58","unstructured":"R Core Team (2020) The R Project for Statistical Computing, Vienna, Austria. In: https:\/\/www.R-project.org\/. Accessed 01 June 2021"},{"key":"2052_CR59","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/978-94-007-0659-0_2","volume-title":"Tumor-associated fibroblasts and their matrix","author":"HP Rodemann","year":"2011","unstructured":"Rodemann HP, Rennekampff H-O (2011) Functional diversity of fibroblasts. Tumor-associated fibroblasts and their matrix. Springer, Dordrecht, pp 23\u201336"},{"key":"2052_CR60","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1038\/nrm2455","volume":"9","author":"M Sch\u00e4fer","year":"2008","unstructured":"Sch\u00e4fer M, Werner S (2008) Cancer as an overhealing wound: an old hypothesis revisited. Nat Rev Mol Cell Biol 9:628\u2013638","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2052_CR61","doi-asserted-by":"publisher","first-page":"125","DOI":"10.4161\/19336918.2014.972781","volume":"9","author":"H Shao","year":"2015","unstructured":"Shao H, Kirkwood JM, Wells A (2015) Tenascin-C signaling in melanoma. Cell Adh Migr 9:125\u2013130","journal-title":"Cell Adh Migr"},{"key":"2052_CR62","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2019.1565264","author":"S Sj\u00f6qvist","year":"2019","unstructured":"Sj\u00f6qvist S, Ishikawa T, Shimura D et al (2019) Exosomes derived from clinical-grade oral mucosal epithelial cell sheets promote wound healing. J Extracell Vesicles. https:\/\/doi.org\/10.1080\/20013078.2019.1565264","journal-title":"J Extracell Vesicles"},{"key":"2052_CR63","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.11069","author":"K Smetana","year":"2016","unstructured":"Smetana K, Lacina L, Szabo P et al (2016) Ageing as an important risk factor for cancer. Anticancer Res. https:\/\/doi.org\/10.21873\/anticanres.11069","journal-title":"Anticancer Res"},{"key":"2052_CR64","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/cancers12092494","volume":"12","author":"K Smetana","year":"2020","unstructured":"Smetana K, Lacina L, Kodet O (2020) Targeted therapies for melanoma. Cancers 12:1\u20134","journal-title":"Cancers"},{"key":"2052_CR65","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1093\/biostatistics\/kxw041","volume":"18","author":"M Stephens","year":"2017","unstructured":"Stephens M (2017) False discovery rates: a new deal. Biostatistics 18:275\u2013294. https:\/\/doi.org\/10.1093\/biostatistics\/kxw041","journal-title":"Biostatistics"},{"key":"2052_CR66","doi-asserted-by":"publisher","DOI":"10.1002\/0471143030.cb0322s30","author":"C Th\u00e9ry","year":"2006","unstructured":"Th\u00e9ry C, Amigorena S, Raposo G, Clayton A (2006) Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol. https:\/\/doi.org\/10.1002\/0471143030.cb0322s30","journal-title":"Curr Protoc Cell Biol"},{"key":"2052_CR67","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1083\/jcb.17.2.299","volume":"17","author":"GJ Todaro","year":"1963","unstructured":"Todaro GJ, Green H (1963) Quantitative studies of the growth of mouse embryo cells in culture and their development into established linesJ. Cell Biol 17:299\u2013313. https:\/\/doi.org\/10.1083\/jcb.17.2.299","journal-title":"Cell Biol"},{"key":"2052_CR68","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1177\/120347540300700208","volume":"7","author":"MJ Trotter","year":"2003","unstructured":"Trotter MJ, Colwell R, Tron VA (2003) Thrombospondin-1 and cutaneous melanoma. J Cutan Med Surg 7:136\u2013141","journal-title":"J Cutan Med Surg"},{"key":"2052_CR69","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/cancers12102923","volume":"12","author":"T Tsering","year":"2020","unstructured":"Tsering T, Laskaris A, Abdouh M et al (2020) Uveal melanoma-derived extracellular vesicles display transforming potential and carry protein cargo involved in metastatic niche preparation. Cancers 12:1\u201325. https:\/\/doi.org\/10.3390\/cancers12102923","journal-title":"Cancers"},{"key":"2052_CR70","doi-asserted-by":"publisher","first-page":"2324","DOI":"10.3390\/cancers12082324","volume":"12","author":"G Valcz","year":"2020","unstructured":"Valcz G, Buz\u00e1s EI, Sebesty\u00e9n A et al (2020) Extracellular vesicle-based communication may contribute to the co-evolution of cancer stem cells and cancer-associated fibroblasts in anti-cancer therapy. Cancers 12:2324. https:\/\/doi.org\/10.3390\/cancers12082324","journal-title":"Cancers"},{"key":"2052_CR71","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1007\/BF00046361","volume":"9","author":"I Vlodavsky","year":"1990","unstructured":"Vlodavsky I, Korner G, Ishai-Michaeli R et al (1990) Extracellular matrix-resident growth factors and enzymes: possible involvement in tumor metastasis and angiogenesis. Cancer Metastasis Rev 9:203\u2013226. https:\/\/doi.org\/10.1007\/BF00046361","journal-title":"Cancer Metastasis Rev"},{"key":"2052_CR72","doi-asserted-by":"publisher","first-page":"2116","DOI":"10.2174\/1381612826666200128091506","volume":"26","author":"P Wang","year":"2020","unstructured":"Wang P, Zeng Z, Lin C et al (2020) Thrombospondin-1 as a potential therapeutic target: multiple roles in cancers. Curr Pharm Des 26:2116\u20132136. https:\/\/doi.org\/10.2174\/1381612826666200128091506","journal-title":"Curr Pharm Des"},{"key":"2052_CR73","doi-asserted-by":"publisher","first-page":"9621","DOI":"10.1158\/0008-5472.CAN-10-1722","volume":"70","author":"J Webber","year":"2010","unstructured":"Webber J, Steadman R, Mason MD et al (2010) Cancer exosomes trigger fibroblast to myofibroblast differentiation. Cancer Res 70:9621\u20139630. https:\/\/doi.org\/10.1158\/0008-5472.CAN-10-1722","journal-title":"Cancer Res"},{"key":"2052_CR74","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.ymeth.2015.04.008","volume":"87","author":"R Xu","year":"2015","unstructured":"Xu R, Greening DW, Rai A et al (2015) Highly-purified exosomes and shed microvesicles isolated from the human colon cancer cell line LIM1863 by sequential centrifugal ultrafiltration are biochemically and functionally distinct. Methods 87:11\u201325. https:\/\/doi.org\/10.1016\/j.ymeth.2015.04.008","journal-title":"Methods"},{"key":"2052_CR75","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-019-2058-1","author":"S Xu","year":"2019","unstructured":"Xu S, Xu H, Wang W et al (2019) The role of collagen in cancer: from bench to bedside. J Transl Med. https:\/\/doi.org\/10.1186\/s12967-019-2058-1","journal-title":"J Transl Med"},{"key":"2052_CR76","doi-asserted-by":"publisher","first-page":"303","DOI":"10.2147\/JIR.S254879","volume":"13","author":"Z Yao","year":"2020","unstructured":"Yao Z, Li J, Wang X et al (2020) Microrna-21-3p engineered umbilical cord stem cell-derived exosomes inhibit tendon adhesion. J Inflamm Res 13:303\u2013316. https:\/\/doi.org\/10.2147\/JIR.S254879","journal-title":"J Inflamm Res"},{"key":"2052_CR77","doi-asserted-by":"publisher","first-page":"D682","DOI":"10.1093\/nar\/gkz966","volume":"48","author":"AD Yates","year":"2020","unstructured":"Yates AD, Achuthan P, Akanni W et al (2020) Ensembl 2020. Nucleic Acids Res 48:D682\u2013D688. https:\/\/doi.org\/10.1093\/nar\/gkz966","journal-title":"Nucleic Acids Res"},{"key":"2052_CR78","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2010-11-2-r14","author":"MD Young","year":"2010","unstructured":"Young MD, Wakefield MJ, Smyth GK, Oshlack A (2010) Gene ontology analysis for RNA-seq: accounting for selection bias. Genome Biol. https:\/\/doi.org\/10.1186\/gb-2010-11-2-r14","journal-title":"Genome Biol"},{"key":"2052_CR79","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2020.12.015","author":"WY Yu","year":"2021","unstructured":"Yu WY, Hill ST, Chan ER et al (2021) Computational drug repositioning identifies statins as modifiers of prognostic genetic expression signatures and metastatic behavior in melanoma. J Invest Dermatol. https:\/\/doi.org\/10.1016\/j.jid.2020.12.015","journal-title":"J Invest Dermatol"},{"key":"2052_CR80","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms21145066","volume":"21","author":"A Zebrowska","year":"2020","unstructured":"Zebrowska A, Widlak P, Whiteside T, Pietrowska M (2020) Signaling of tumor-derived sev impacts melanoma progression. Int J Mol Sci 21:1\u201321","journal-title":"Int J Mol Sci"},{"key":"2052_CR81","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.1038\/s41388-019-1078-x","volume":"39","author":"Q Zhou","year":"2020","unstructured":"Zhou Q, Wu X, Wang X et al (2020) The reciprocal interaction between tumor cells and activated fibroblasts mediated by TNF-\u03b1\/IL-33\/ST2L signaling promotes gastric cancer metastasis. Oncogene 39:1414\u20131428. https:\/\/doi.org\/10.1038\/s41388-019-1078-x","journal-title":"Oncogene"}],"container-title":["Histochemistry and Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00418-021-02052-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00418-021-02052-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00418-021-02052-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T05:05:01Z","timestamp":1644901501000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00418-021-02052-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,27]]},"references-count":81,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["2052"],"URL":"https:\/\/doi.org\/10.1007\/s00418-021-02052-2","relation":{},"ISSN":["0948-6143","1432-119X"],"issn-type":[{"value":"0948-6143","type":"print"},{"value":"1432-119X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,27]]},"assertion":[{"value":"5 November 2021","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 November 2021","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All authors declare no conflicting\/competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Tissues for fibroblast isolations were collected after local ethics committee approval following the ethical standards of the Institutional and National Research Committee and according to the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The patient\u2019s informed consent was obtained.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}