{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T09:49:59Z","timestamp":1765792199408,"version":"3.48.0"},"reference-count":83,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"publisher","award":["NKFIHK139396"],"award-info":[{"award-number":["NKFIHK139396"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"publisher","award":["K135457"],"award-info":[{"award-number":["K135457"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"publisher","award":["TKP2021-EGA-32"],"award-info":[{"award-number":["TKP2021-EGA-32"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"publisher","award":["National Brain Research Program NAP3"],"award-info":[{"award-number":["National Brain Research Program NAP3"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"name":"HUN-REN Research Centre for Natural Sciences","award":["HUN-REN TKI14016"],"award-info":[{"award-number":["HUN-REN TKI14016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pituitary adenylate cyclase-activating polypeptide (PACAP) is a small neuropeptide detected first in the hypothalamo\u2013hypophyseal system; recently, it has also been identified in peripheral organs and in tumours. It is well demonstrated that PACAP exerts cell- and tissue-protecting effects in various stressful conditions and helps to maintain tissue homeostasis. In melanoma, the anti-invasive effect of PACAP has been demonstrated; however, there is also existing sporadic data which proves PACAP plays a role in melanoma progression. The major goal of our study was to investigate the signalling targets of PACAP in A2058 and WM35 melanoma cell lines in vitro. Various molecular players of melanocyte differentiation and function responded to PACAP application. SOX9 expression increased while SOX10 expression decreased and CREB signalling did not change. The expression level of TYRP1 decreased, while DCT elevated, and MITF expression showed changes at the mRNA level and in its subcellular localisation. In contrast, the amount of hyaluronan (HA) and expressions of its synthases, as well as RHAMM, increased, indicating the role of PACAP in secretion of an HA-rich matrix. In parallel with these results, we detected elevated hyaluronidase2 (Hyal2) expression in the presence of PACAP. On the other hand, alfaV and beta3 integrin expressions did not alter significantly. Our results demonstrate that exogenous PACAP modulates the expression of multiple target molecules in melanoma cells. Some of the significantly responding molecules take part in hyaluronan homeostasis, suggesting an effect of PACAP on tumour matrix composition, through which it can modulate invasiveness of melanoma cells.<\/jats:p>","DOI":"10.3390\/ijms262412049","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T09:36:39Z","timestamp":1765791399000},"page":"12049","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the Link Between PACAP Signalling and Hyaluronic Acid Production in Melanoma Progression"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9954-1987","authenticated-orcid":false,"given":"Tibor","family":"Hajd\u00fa","sequence":"first","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1588-7962","authenticated-orcid":false,"given":"Patrik","family":"Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c9va","family":"Katona","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minh Ngoc","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judit","family":"V\u00e1g\u00f3","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Csaba","family":"Fill\u00e9r","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R\u00f3za","family":"Z\u00e1k\u00e1ny","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2877-4740","authenticated-orcid":false,"given":"Gabriella","family":"Emri","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00e1bor","family":"T\u00f3th","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Dom t\u00e9r 8, H-6720 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D\u00f3ra","family":"Regl\u0151di","sequence":"additional","affiliation":[{"name":"Department of Anatomy, HUN-REN-PTE PACAP Research Team, Medical School, University of P\u00e9cs, Szigeti \u00fat 12, H-7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0489-5676","authenticated-orcid":false,"given":"Tam\u00e1s","family":"Juh\u00e1sz","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.jaad.2024.09.035","article-title":"Global trends in melanoma burden: A comprehensive analysis from the Global Burden of Disease Study, 1990\u20132021","volume":"92","author":"Sun","year":"2025","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"330e","DOI":"10.1097\/PRS.0000000000002367","article-title":"Malignant Melanoma: Beyond the Basics","volume":"138","author":"Pavri","year":"2016","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1097\/00008390-200008000-00001","article-title":"Lessons from melanocyte development for understanding the biological events in naevus and melanoma formation","volume":"10","author":"Herlyn","year":"2000","journal-title":"Melanoma Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"dev201266","DOI":"10.1242\/dev.201266","article-title":"Melanocyte lineage dynamics in development, growth and disease","volume":"151","author":"Brombin","year":"2024","journal-title":"Development"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Koczkodaj, P., Sulkowska, U., Didkowska, J., Rutkowski, P., and Manczuk, M. (2023). Melanoma Mortality Trends in 28 European Countries: A Retrospective Analysis for the Years 1960\u20132020. Cancers, 15.","DOI":"10.3390\/cancers15051514"},{"key":"ref_6","first-page":"1005","article-title":"Melanoma: Epidemiology, risk factors, pathogenesis, diagnosis and classification","volume":"28","author":"Rastrelli","year":"2014","journal-title":"In Vivo"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e2020033","DOI":"10.5826\/dpc.1003a33","article-title":"Melanoma Epidemiology and Early Detection in Europe: Diversity and Disparities","volume":"10","author":"Forsea","year":"2020","journal-title":"Dermatol. Pr. Concept."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.pathol.2015.12.002","article-title":"Melanoma progression","volume":"48","author":"Elder","year":"2016","journal-title":"Pathology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1111\/j.1365-4632.2010.04474.x","article-title":"Ultraviolet radiation and skin cancer","volume":"49","author":"Narayanan","year":"2010","journal-title":"Int. J. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.cell.2012.06.024","article-title":"A landscape of driver mutations in melanoma","volume":"150","author":"Hodis","year":"2012","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"adv00138","DOI":"10.2340\/00015555-3493","article-title":"Melanoma Genomics","volume":"100","author":"Bishop","year":"2020","journal-title":"Acta Derm. Venereol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.semcancer.2019.08.002","article-title":"Unraveling the crosstalk between melanoma and immune cells in the tumor microenvironment","volume":"59","author":"Marzagalli","year":"2019","journal-title":"Semin. Cancer Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.5858\/2001-125-1295-MM","article-title":"Malignant melanoma","volume":"125","author":"Slominski","year":"2001","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.cps.2021.05.002","article-title":"Canonical Signaling Pathways in Melanoma","volume":"48","author":"Sun","year":"2021","journal-title":"Clin. Plast. Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"983","DOI":"10.3892\/ijo.2015.3313","article-title":"PP2B and ERK1\/2 regulate hyaluronan synthesis of HT168 and WM35 human melanoma cell lines","volume":"48","author":"Katona","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Takabe, P., Siiskonen, H., Ronka, A., Kainulainen, K., and Pasonen-Seppanen, S. (2021). The Impact of Hyaluronan on Tumor Progression in Cutaneous Melanoma. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.811434"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"C145","DOI":"10.1152\/ajpcell.00139.2022","article-title":"Hyaluronan network: A driving force in cancer progression","volume":"323","author":"Karalis","year":"2022","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chanmee, T., Ontong, P., Kimata, K., and Itano, N. (2015). Key Roles of Hyaluronan and Its CD44 Receptor in the Stemness and Survival of Cancer Stem Cells. Front. Oncol., 5.","DOI":"10.3389\/fonc.2015.00180"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13045-018-0605-5","article-title":"The biology and role of CD44 in cancer progression: Therapeutic implications","volume":"11","author":"Chen","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/978-3-030-36214-0_10","article-title":"Tumour Microenvironment in Skin Carcinogenesis","volume":"1226","author":"Georgescu","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Hassn Mesrati, M., Syafruddin, S.E., Mohtar, M.A., and Syahir, A. (2021). CD44: A Multifunctional Mediator of Cancer Progression. Biomolecules, 11.","DOI":"10.3390\/biom11121850"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Gebhardt, C., Averbeck, M., Anderegg, U., and Simon, J.C. (2009). Role of Hyaluronan and CD44 in Melanoma Progression. Hyaluronan in Cancer Biology, Academic Press. [1st ed.].","DOI":"10.1016\/B978-012374178-3.10017-1"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Siiskonen, H., Poukka, M., Tyynela-Korhonen, K., Sironen, R., and Pasonen-Seppanen, S. (2013). Inverse expression of hyaluronidase 2 and hyaluronan synthases 1-3 is associated with reduced hyaluronan content in malignant cutaneous melanoma. BMC Cancer, 13.","DOI":"10.1186\/1471-2407-13-181"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1124\/pr.109.001370","article-title":"Pituitary adenylate cyclase-activating polypeptide and its receptors: 20 years after the discovery","volume":"61","author":"Vaudry","year":"2009","journal-title":"Pharmacol. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/0006-291X(89)91757-9","article-title":"Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells","volume":"164","author":"Miyata","year":"1989","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1196\/annals.1317.018","article-title":"PACAP, VIP, and PHI: Effects on AC-, PLC-, and PLD-driven signaling systems in the primary glial cell cultures","volume":"1070","author":"Dejda","year":"2006","journal-title":"Ann. N. Y Acad. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.peptides.2015.02.001","article-title":"PACAP and VIP signaling in chondrogenesis and osteogenesis","volume":"66","author":"Juhasz","year":"2015","journal-title":"Peptides"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Denes, V., Geck, P., Mester, A., and Gabriel, R. (2019). Pituitary Adenylate Cyclase-Activating Polypeptide: 30 Years in Research Spotlight and 600 Million Years in Service. J. Clin. Med., 8.","DOI":"10.3390\/jcm8091488"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Hajdu, T., Kovacs, P., Zsigrai, E., Takacs, R., Vago, J., Cho, S., Sasi-Szabo, L., Becsky, D., Keller-Pinter, A., and Emri, G. (2021). Pituitary Adenylate Cyclase Activating Polypeptide Has Inhibitory Effects on Melanoma Cell Proliferation and Migration In Vitro. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.681603"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/j.1749-6632.2003.tb03145.x","article-title":"PACAP in immunity and inflammation","volume":"992","author":"Delgado","year":"2003","journal-title":"Ann. N. Y Acad. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1016\/S0196-9781(96)00171-4","article-title":"Pituitary adenylate cyclase-activating polypeptide (PACAP-38) stimulates rat peritoneal macrophage functions","volume":"17","author":"Delgado","year":"1996","journal-title":"Peptides"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1111\/j.1755-148X.2010.00711.x","article-title":"Sox proteins in melanocyte development and melanoma","volume":"23","author":"Harris","year":"2010","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1007\/s00018-014-1791-0","article-title":"MITF in melanoma: Mechanisms behind its expression and activity","volume":"72","author":"Hartman","year":"2015","journal-title":"Cell Mol. Life Sci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lee, S., Park, J., Cho, S., Kim, E.J., Oh, S., Lee, Y., Park, S., Kang, K., Shin, D.H., and Ko, S.Y. (2025). Hyaluronan network remodeling by ZEB1 and ITIH2 enhances the motility and invasiveness of cancer cells. J. Clin. Invest., 135.","DOI":"10.1172\/JCI180570"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Juhasz, T., Matta, C., Katona, E., Somogyi, C., Takacs, R., Gergely, P., Csernoch, L., Panyi, G., Toth, G., and Reglodi, D. (2014). Pituitary adenylate cyclase activating polypeptide (PACAP) signalling exerts chondrogenesis promoting and protecting effects: Implication of calcineurin as a downstream target. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091541"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"345","DOI":"10.3389\/fendo.2018.00345","article-title":"Neuropeptide G Protein-Coupled Receptors as Oncotargets","volume":"9","author":"Moody","year":"2018","journal-title":"Front Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Maugeri, G., D\u2019Amico, A.G., Saccone, S., Federico, C., Rasa, D.M., Caltabiano, R., Broggi, G., Giunta, S., Musumeci, G., and D\u2019Agata, V. (2021). Effect of PACAP on Hypoxia-Induced Angiogenesis and Epithelial-Mesenchymal Transition in Glioblastoma. Biomedicines, 9.","DOI":"10.3390\/biomedicines9080965"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1080\/09513590500098240","article-title":"Pituitary adenylate cyclase-activating peptide\/vasoactive intestinal peptide receptors in human normal mammary gland and breast cancer tissue","volume":"20","author":"Collado","year":"2005","journal-title":"Gynecol. Endocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1159\/000067180","article-title":"Pituitary adenylate-cyclase-activating polypeptide expression in the immune system","volume":"10","author":"Abad","year":"2002","journal-title":"Neuroimmunomodulation"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"657","DOI":"10.3724\/abbs.2022041","article-title":"Positive allosteric regulation of PAC1-R up-regulates PAC1-R and its specific ligand PACAP","volume":"54","author":"Fan","year":"2022","journal-title":"Acta Biochim Biophys Sin."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3316","DOI":"10.1074\/jbc.RA119.010004","article-title":"A tripartite cooperative mechanism confers resistance of the protein kinase A catalytic subunit to dephosphorylation","volume":"295","author":"Chan","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1177\/154411130201300303","article-title":"Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) as modulators of both innate and adaptive immunity","volume":"13","author":"Ganea","year":"2002","journal-title":"Crit. Rev. Oral. Biol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1210\/en.2002-221009","article-title":"Dual effect of pituitary adenylate cyclase activating polypeptide on prostate tumor LNCaP cells: Short- and long-term exposure affect proliferation and neuroendocrine differentiation","volume":"144","author":"Farini","year":"2003","journal-title":"Endocrinology"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Shakhova, O., Cheng, P., Mishra, P.J., Zingg, D., Schaefer, S.M., Debbache, J., Hausel, J., Matter, C., Guo, T., and Davis, S. (2015). Antagonistic cross-regulation between Sox9 and Sox10 controls an anti-tumorigenic program in melanoma. PLoS Genet., 11.","DOI":"10.1371\/journal.pgen.1004877"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"110085","DOI":"10.1016\/j.celrep.2021.110085","article-title":"SOX10 requirement for melanoma tumor growth is due, in part, to immune-mediated effects","volume":"37","author":"Rosenbaum","year":"2021","journal-title":"Cell Rep."},{"key":"ref_46","first-page":"954","article-title":"Upregulation of SOX9 inhibits the growth of human and mouse melanomas and restores their sensitivity to retinoic acid","volume":"119","author":"Passeron","year":"2009","journal-title":"J. Clin. Invest."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3024","DOI":"10.1038\/sj.onc.1206442","article-title":"The importance of having your SOX on: Role of SOX10 in the development of neural crest-derived melanocytes and glia","volume":"22","author":"Mollaaghababa","year":"2003","journal-title":"Oncogene"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s10555-016-9613-5","article-title":"Genetic progression of malignant melanoma","volume":"35","author":"Timar","year":"2016","journal-title":"Cancer Metastasis Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.ccr.2006.04.021","article-title":"Oncogenic MITF dysregulation in clear cell sarcoma: Defining the MiT family of human cancers","volume":"9","author":"Davis","year":"2006","journal-title":"Cancer Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1046\/j.1523-1747.2000.00023.x","article-title":"Human melanocytes and melanomas express novel mRNA isoforms of the tyrosinase-related protein-2\/DOPAchrome tautomerase gene: Molecular and functional characterization","volume":"115","author":"Pisarra","year":"2000","journal-title":"J. Invest. Dermatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1097\/CJI.0b013e31819144d7","article-title":"Melanoma progression despite infiltration by in vivo-primed TRP-2-specific T cells","volume":"32","author":"Singh","year":"2009","journal-title":"J. Immunother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1111\/j.1600-0749.1998.tb00723.x","article-title":"Human melanoma cell lines show little relationship between expression of pigmentation genes and pigmentary behaviour in vitro","volume":"11","author":"Eberle","year":"1998","journal-title":"Pigment. Cell Res."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Militaru, I.V., Rus, A.A., Munteanu, C.V.A., Manica, G., and Petrescu, S.M. (2022). New panel of biomarkers to discriminate between amelanotic and melanotic metastatic melanoma. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1061832"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1038\/bjc.2011.451","article-title":"TYRP1 mRNA expression in melanoma metastases correlates with clinical outcome","volume":"105","author":"Journe","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/978-3-030-40146-7_3","article-title":"Hyaluronan in the Tumor Microenvironment","volume":"1245","author":"Spinelli","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.yexcr.2010.11.017","article-title":"Hyaluronan in human malignancies","volume":"317","author":"Sironen","year":"2011","journal-title":"Exp. Cell Res."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Mayasin, Y.P., Osinnikova, M.N., Kharisova, C.B., Kitaeva, K.V., Filin, I.Y., Gorodilova, A.V., Kutovoi, G.I., Solovyeva, V.V., Golubev, A.I., and Rizvanov, A.A. (2024). Extracellular Matrix as a Target in Melanoma Therapy: From Hypothesis to Clinical Trials. Cells, 13.","DOI":"10.20944\/preprints202410.1515.v1"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1046\/j.1523-1747.2001.00236.x","article-title":"CD44 is the principal mediator of hyaluronic-acid-induced melanoma cell proliferation","volume":"116","author":"Ahrens","year":"2001","journal-title":"J. Invest. Dermatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3383","DOI":"10.1007\/s11010-021-04165-7","article-title":"Hyaluronan synthase 2 (HAS2) regulates cell phenotype and invadopodia formation in luminal-like breast cancer cells","volume":"476","author":"Sheng","year":"2021","journal-title":"Mol. Cell Biochem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.yexcr.2015.07.026","article-title":"Hyaluronan synthase 3 (HAS3) overexpression downregulates MV3 melanoma cell proliferation, migration and adhesion","volume":"337","author":"Takabe","year":"2015","journal-title":"Exp. Cell Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1002\/ijc.25460","article-title":"HYAL1 overexpression is correlated with the malignant behavior of human breast cancer","volume":"128","author":"Tan","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"7782","DOI":"10.1158\/0008-5472.CAN-05-1022","article-title":"HYAL1 hyaluronidase in prostate cancer: A tumor promoter and suppressor","volume":"65","author":"Lokeshwar","year":"2005","journal-title":"Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"13144","DOI":"10.1074\/jbc.M115.647446","article-title":"Hyaluronidase Hyal1 Increases Tumor Cell Proliferation and Motility through Accelerated Vesicle Trafficking","volume":"290","author":"McAtee","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.bbrc.2011.06.125","article-title":"Hyal2 is a glycosylphosphatidylinositol-anchored, lipid raft-associated hyaluronidase","volume":"411","author":"Andre","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1111\/jgh.14660","article-title":"The suppressive role of HYAL1 and HYAL2 in the metastasis of colorectal cancer","volume":"34","author":"Jin","year":"2019","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1096\/fj.14-259978","article-title":"A novel role of low molecular weight hyaluronan in breast cancer metastasis","volume":"29","author":"Wu","year":"2015","journal-title":"FASEB J."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Liu, J.P., Fang, Y.T., Jiang, Y.F., and Lin, H. (2022). HYAL3 as a potential novel marker of BLCA patient prognosis. BMC Genom. Data, 23.","DOI":"10.1186\/s12863-022-01070-w"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4410","DOI":"10.1158\/1078-0432.CCR-21-0422","article-title":"HYAL4-V1\/Chondroitinase (Chase) Drives Gemcitabine Resistance and Predicts Chemotherapy Failure in Patients with Bladder Cancer","volume":"27","author":"Hasanali","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1111\/ijd.14850","article-title":"The role of integrins in melanoma: A review","volume":"59","author":"Warda","year":"2020","journal-title":"Int. J. Dermatol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1189\/jlb.0507327","article-title":"VIP differentially activates beta2 integrins, CR1, and matrix metalloproteinase-9 in human monocytes through cAMP\/PKA, EPAC, and PI-3K signaling pathways via VIP receptor type 1 and FPRL1","volume":"83","author":"Badran","year":"2008","journal-title":"J. Leukoc. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s13046-018-0763-x","article-title":"Integrins as therapeutic targets in the organ-specific metastasis of human malignant melanoma","volume":"37","author":"Huang","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.bone.2010.09.016","article-title":"Integrins and bone metastasis: Integrating tumor cell and stromal cell interactions","volume":"48","author":"Schneider","year":"2011","journal-title":"Bone"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1097\/MED.0000000000000218","article-title":"Vasoactive intestinal peptide\/pituitary adenylate cyclase activating polypeptide, and their receptors and cancer","volume":"23","author":"Moody","year":"2016","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1016\/j.pharep.2018.05.005","article-title":"Involvement of vascular endothelial growth factor (VEGF) and mitogen-activated protein kinases (MAPK) in the mechanism of neuroleptic drugs","volume":"70","author":"Kowalczyk","year":"2018","journal-title":"Pharmacol. Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0167-0115(02)00194-5","article-title":"PAC1 and PACAP expression, signaling, and effect on the growth of HCT8, human colonic tumor cells","volume":"109","author":"Le","year":"2002","journal-title":"Regul. Pept."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4730","DOI":"10.1016\/j.febslet.2014.11.004","article-title":"PACAP inhibits tumor growth and interferes with clusterin in cervical carcinomas","volume":"588","author":"Lee","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Langer, I., Jeandriens, J., Couvineau, A., Sanmukh, S., and Latek, D. (2022). Signal Transduction by VIP and PACAP Receptors. Biomedicines, 10.","DOI":"10.3390\/biomedicines10020406"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1007\/s10571-010-9594-9","article-title":"Expression of trophic peptides and their receptors in chromaffin cells and pheochromocytoma","volume":"30","author":"Thouennon","year":"2010","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1007\/s12031-013-0076-7","article-title":"Antiproliferative effects of PACAP and VIP in serum-starved glioma cells","volume":"51","author":"Scuderi","year":"2013","journal-title":"J. Mol. Neurosci."},{"key":"ref_80","first-page":"3105","article-title":"Vasoactive intestinal peptide\/pituitary adenylate cyclase-activating peptide receptor subtypes in human tumors and their tissues of origin","volume":"60","author":"Reubi","year":"2000","journal-title":"Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/978-1-0716-4434-8_6","article-title":"Isolation of the Surfaceome from Primary Human Epidermal Melanocytes Using Glycocapture and Shotgun Proteomics","volume":"2908","author":"Hajdu","year":"2025","journal-title":"Methods Mol. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1002\/ijc.2910460224","article-title":"Modulation of type-IV collagenase activity and invasive behavior of metastatic human melanoma (A2058) cells in vitro by monoclonal antibodies to type-IV collagenase","volume":"46","author":"Hoyhtya","year":"1990","journal-title":"Int. J. Cancer"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4480","DOI":"10.1038\/sj.onc.1203808","article-title":"UVB induced cell cycle checkpoints in an early stage human melanoma line, WM35","volume":"19","author":"Petrocelli","year":"2000","journal-title":"Oncogene"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/12049\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T09:48:07Z","timestamp":1765792087000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/12049"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,15]]},"references-count":83,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262412049"],"URL":"https:\/\/doi.org\/10.3390\/ijms262412049","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,15]]}}}