{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T10:59:47Z","timestamp":1762253987312,"version":"build-2065373602"},"reference-count":73,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T00:00:00Z","timestamp":1638489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/MED-TOX\/29183\/2017","UIDB\/04138\/2020","UIDP\/04138\/2020","UID\/IC\/00051\/2019","UID\/BIM\/04501\/2020","UIDB\/50006\/2020","IF\/00286\/2015"],"award-info":[{"award-number":["PTDC\/MED-TOX\/29183\/2017","UIDB\/04138\/2020","UIDP\/04138\/2020","UID\/IC\/00051\/2019","UID\/BIM\/04501\/2020","UIDB\/50006\/2020","IF\/00286\/2015"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011929","name":"Programa Operacional Tem\u00e1tico Factores de Competitividade","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-007628"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007628"]}],"id":[{"id":"10.13039\/501100011929","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Doxorubicin (Dox) is one of the most widely used treatments for breast cancer, although limited by the well-documented cardiotoxicity and other off-target effects. Mesenchymal stem cell (MSC) secretome has shown immunomodulatory and regenerative properties, further potentiated under 3D conditions. This work aimed to uncover the effect of the MSC-derived secretome from 3D (CM3D) or 2D (CM2D) cultures, in human malignant breast cells (MDA-MB-231), non-tumor breast epithelial cells (MCF10A) and differentiated AC16 cardiomyocytes, co-treated with Dox. A comprehensive proteomic analysis of CM3D\/CM2D was also performed to unravel the underlying mechanism. CM3D\/CM2D co-incubation with Dox revealed no significant differences in MDA-MB-231 viability when compared to Dox alone, whereas MCF10A and AC16 viability was consistently improved in Dox+CM3D-treated cells. Moreover, neither CM2D nor CM3D affected Dox anti-migratory and anti-invasive effects in MDA-MB-231. Notably, Ge-LC-MS\/MS proteomic analysis revealed that CM3D displayed protective features that might be linked to the regulation of cell proliferation (CAPN1, CST1, LAMC2, RANBP3), migration (CCN3, MMP8, PDCD5), invasion (TIMP1\/2), oxidative stress (COX6B1, AIFM1, CD9, GSR) and inflammation (CCN3, ANXA5, CDH13, GDF15). Overall, CM3D decreased Dox-induced cytotoxicity in non-tumor cells, without compromising Dox chemotherapeutic profile in malignant cells, suggesting its potential use as a chemotherapy adjuvant to reduce off-target side effects.<\/jats:p>","DOI":"10.3390\/ijms222313072","type":"journal-article","created":{"date-parts":[[2021,12,5]],"date-time":"2021-12-05T21:01:45Z","timestamp":1638738105000},"page":"13072","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Secretome of Human Neonatal Mesenchymal Stem Cells Modulates Doxorubicin-Induced Cytotoxicity: Impact in Non-Tumor Cells"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7941-9511","authenticated-orcid":false,"given":"Ana S.","family":"Serras","sequence":"first","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0355-5338","authenticated-orcid":false,"given":"S\u00e9rgio P.","family":"Cam\u00f5es","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4423-0460","authenticated-orcid":false,"given":"Bernardo","family":"Antunes","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0471-2756","authenticated-orcid":false,"given":"Vera M.","family":"Costa","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6175-0479","authenticated-orcid":false,"given":"Fl\u00e1vio","family":"Dion\u00edsio","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3861-0181","authenticated-orcid":false,"given":"Volkan","family":"Yazar","sequence":"additional","affiliation":[{"name":"Institute for Cell Engineering, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3636-5805","authenticated-orcid":false,"given":"Rui","family":"Vitorino","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Mass Spectrometry Center, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"},{"name":"Cardiovascular R&D Center, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, 4200-319 Oporto, Portugal"},{"name":"iBiMED, Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1382-5119","authenticated-orcid":false,"given":"Fernando","family":"Remi\u00e3o","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6314-8251","authenticated-orcid":false,"given":"Matilde","family":"Castro","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6114-6829","authenticated-orcid":false,"given":"Nuno G.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7804-4068","authenticated-orcid":false,"given":"Joana P.","family":"Miranda","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"438","DOI":"10.3322\/caac.21583","article-title":"Breast cancer statistics, 2019","volume":"69","author":"DeSantis","year":"2019","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"224","DOI":"10.3816\/CBC.2008.n.025","article-title":"Metastatic breast cancer: The treatment challenge","volume":"8","author":"Jones","year":"2008","journal-title":"Clin. Breast Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1136\/heartjnl-2017-312103","article-title":"Anthracycline cardiotoxicity: An update on mechanisms, monitoring and prevention","volume":"104","author":"Henriksen","year":"2018","journal-title":"Heart"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/j.2042-7158.2012.01567.x","article-title":"Doxorubicin: An update on anticancer molecular action, toxicity and novel drug delivery systems","volume":"65","author":"Tacar","year":"2012","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Marinello, J., Delcuratolo, M., and Capranico, G. (2018). Anthracyclines as Topoisomerase II Poisons: From Early Studies to New Perspectives. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113480"},{"key":"ref_6","first-page":"15","article-title":"Anthracycline-induced cardiotoxicity in the chemotherapy treatment of breast cancer: Preventive strategies and treatment","volume":"11","author":"Cai","year":"2019","journal-title":"Mol. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"75","DOI":"10.2174\/1389200216666151103114926","article-title":"The Role of the Metabolism of Anticancer Drugs in Their Induced-Cardiotoxicity","volume":"17","author":"Sousa","year":"2015","journal-title":"Curr. Drug Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/clpt.2012.96","article-title":"Pharmacogenomics Knowledge for Personalized Medicine","volume":"92","author":"McDonagh","year":"2012","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1080\/03602532.2017.1316285","article-title":"The importance of drug metabolites synthesis: The case-study of cardiotoxic anticancer drugs","volume":"49","author":"Hrynchak","year":"2017","journal-title":"Drug Metab. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.lfs.2018.03.023","article-title":"Toxicity of Doxorubicin (Dox) to different experimental organ systems","volume":"200","author":"Pugazhendhi","year":"2018","journal-title":"Life Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"635","DOI":"10.3389\/fphar.2019.00635","article-title":"Mesenchymal stem cell therapy for doxorubicin-induced cardiomyopathy: Potential mechanisms, governing factors, and implications of the heart stem cell debate","volume":"10","author":"Abushouk","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.arr.2012.10.004","article-title":"Oxidative stress and cancer: An overview","volume":"12","author":"Sosa","year":"2013","journal-title":"Ageing Res. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"84559","DOI":"10.18632\/oncotarget.19187","article-title":"Novel strategies to prevent the development of multidrug resistance (MDR) in cancer","volume":"8","author":"Wang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"42740","DOI":"10.18632\/oncotarget.8600","article-title":"Cancer drug resistance: Redox resetting renders a way","volume":"7","author":"Liu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1479-5876-11-18","article-title":"The role of human umbilical cord tissue-derived mesenchymal stromal cells (UCX\u00ae) in the treatment of inflammatory arthritis","volume":"11","author":"Santos","year":"2013","journal-title":"J. Transl. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s13287-015-0082-5","article-title":"Three-dimensional spheroid cell culture of umbilical cord tissue-derived mesenchymal stromal cells leads to enhanced paracrine induction of wound healing","volume":"6","author":"Santos","year":"2015","journal-title":"Stem Cell Res. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/scrt394","article-title":"Human umbilical cord tissue-derived mesenchymal stromal cells attenuate remodeling after myocardial infarction by proangiogenic, antiapoptotic, and endogenous cell-activation mechanisms","volume":"5","author":"Nascimento","year":"2014","journal-title":"Stem Cell Res. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3389\/fimmu.2019.00018","article-title":"The secretome derived from 3D-cultured umbilical cord tissue MSCs counteracts manifestations typifying rheumatoid arthritis","volume":"10","author":"Miranda","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"821","DOI":"10.2217\/fon-2016-0264","article-title":"The role of mesenchymal stem cells in oncology and regenerative medicine","volume":"13","author":"Khan","year":"2017","journal-title":"Futur. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/nature06188","article-title":"Mesenchymal stem cells within tumour stroma promote breast cancer metastasis","volume":"449","author":"Karnoub","year":"2007","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.canlet.2009.02.022","article-title":"Human mesenchymal stem cells (hMSCs) target osteosarcoma and promote its growth and pulmonary metastasis","volume":"281","author":"Xu","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1002\/dvdy.24583","article-title":"Mesenchymal stromal cell engagement in cancer cell epithelial to mesenchymal transition","volume":"247","author":"Bugarski","year":"2018","journal-title":"Dev. Dyn."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11823","DOI":"10.2147\/CMAR.S277130","article-title":"Adipose-Derived Stem Cells Promote Proliferation and Invasion in Cervical Cancer by Targeting the HGF\/c-MET Pathway","volume":"12","author":"Zhai","year":"2020","journal-title":"Cancer Manag. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"737","DOI":"10.2147\/OTT.S283459","article-title":"Bone Marrow Mesenchymal Stem Cells-Derived Extracellular Vesicles Promote Proliferation, Invasion and Migration of Osteosarcoma Cells via the lncRNA MALAT1\/miR-143\/NRSN2\/Wnt\/\u03b2-Catenin Axis","volume":"14","author":"Li","year":"2021","journal-title":"OncoTargets Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.canlet.2009.02.011","article-title":"Na\u00efve human umbilical cord matrix derived stem cells significantly attenuate growth of human breast cancer cells in vitro and in vivo","volume":"280","author":"Ayuzawa","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12015-010-9166-x","article-title":"Human Wharton\u2019s Jelly Stem Cells Have Unique Transcriptome Profiles Compared to Human Embryonic Stem Cells and Other Mesenchymal Stem Cells","volume":"7","author":"Fong","year":"2011","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1002\/jcb.24073","article-title":"Human umbilical cord wharton\u2019s jelly stem cell (hWJSC) extracts inhibit cancer cell growth in vitro","volume":"113","author":"Gauthaman","year":"2012","journal-title":"J. Cell. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1089\/scd.2012.0486","article-title":"Umbilical Cord Blood-Derived Mesenchymal Stem Cells Inhibit, But Adipose Tissue-Derived Mesenchymal Stem Cells Promote, Glioblastoma Multiforme Proliferation","volume":"22","author":"Akimoto","year":"2013","journal-title":"Stem Cells Dev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1002\/mc.22178","article-title":"Mesenchymal stem cells inhibit breast cancer cell migration and invasion through secretion of tissue inhibitor of metalloproteinase-1 and -2","volume":"54","author":"Clarke","year":"2015","journal-title":"Mol. Carcinog."},{"key":"ref_30","first-page":"8536","article-title":"Suppression of tumor cell proliferation and migration by human umbilical cord mesenchymal stem cells: A possible role for apoptosis and Wnt signaling","volume":"15","author":"Yuan","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_31","first-page":"945","article-title":"Human Wharton\u2019s jelly mesenchymal stem cells-derived secretome could inhibit breast cancer growth in vitro and in vivo","volume":"23","author":"Mirabdollahi","year":"2020","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1002\/jcb.24057","article-title":"Human umbilical cord Wharton\u2019s jelly mesenchymal stem cells do not transform to tumor-associated fibroblasts in the presence of breast and ovarian cancer cells unlike bone marrow mesenchymal stem cells","volume":"113","author":"Subramanian","year":"2012","journal-title":"J. Cell. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1007\/s13233-016-4107-4","article-title":"Superiority of three-dimensional stem cell clusters over monolayer culture: An archetype to biological application","volume":"24","author":"Regmi","year":"2016","journal-title":"Macromol. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.yjmcc.2005.03.003","article-title":"Novel cell lines derived from adult human ventricular cardiomyocytes","volume":"39","author":"Davidson","year":"2005","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"11235","DOI":"10.1038\/srep11235","article-title":"Potent Paracrine Effects of human induced Pluripotent Stem Cell-derived Mesenchymal Stem Cells Attenuate Doxorubicin-induced Cardiomyopathy","volume":"5","author":"Zhang","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_36","first-page":"134","article-title":"Effect of human Wharton\u2019s jelly mesenchymal stem cell secretome on proliferation, apoptosis and drug resistance of lung cancer cells","volume":"10","author":"Hendijani","year":"2015","journal-title":"Res. Pharm. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Scotland, P.B., Heath, J.L., Conway, A.E., Porter, N.B., Armstrong, M.B., Walker, J.A., Klebig, M.L., Lavau, C.P., and Wechsler, D.S. (2012). The PICALM Protein Plays a Key Role in Iron Homeostasis and Cell Proliferation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044252"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3121","DOI":"10.1242\/jcs.017996","article-title":"Integrin-linked kinase\u2014Essential roles in physiology and cancer biology","volume":"121","author":"McDonald","year":"2008","journal-title":"J. Cell Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1093\/qjmed\/hcq148","article-title":"Inflammation and cancer: Macrophage migration inhibitory factor (MIF)-the potential missing link","volume":"103","author":"Conroy","year":"2010","journal-title":"QJM"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.3892\/or.2017.5555","article-title":"MicroRNA-329-3p targets MAPK1 to suppress cell proliferation, migration and invasion in cervical cancer","volume":"37","author":"Li","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.canlet.2017.10.018","article-title":"Macrophage migration inhibitory factor promotes tumor aggressiveness of esophageal squamous cell carcinoma via activation of Akt and inactivation of GSK3\u03b2","volume":"412","author":"Liu","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3926","DOI":"10.7150\/jca.31345","article-title":"GPC6 promotes cell proliferation, migration, and invasion in nasopharyngeal carcinoma","volume":"10","author":"Fan","year":"2019","journal-title":"J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.devcel.2009.01.022","article-title":"Nuclear Export of Smad2 and Smad3 by RanBP3 Facilitates Termination of TGF-\u03b2 Signaling","volume":"16","author":"Dai","year":"2009","journal-title":"Dev. Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1111\/brv.12686","article-title":"Calpain\u2013calpastatin system and cancer progression","volume":"96","author":"Nian","year":"2021","journal-title":"Biol. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1038\/bjc.2013.607","article-title":"Tumour-suppressive microRNA-29s inhibit cancer cell migration and invasion by targeting laminin-integrin signalling in head and neck squamous cell carcinoma","volume":"109","author":"Kinoshita","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"11359","DOI":"10.2147\/OTT.S234328","article-title":"Cystatin SN affects cell proliferation by regulating the ER\u03b1\/PI3K\/AKT\/ER\u03b1 loopback pathway in breast cancer","volume":"12","author":"Liu","year":"2019","journal-title":"OncoTargets Ther."},{"key":"ref_47","first-page":"2319","article-title":"The Akt pathway in oncology therapy and beyond (Review)","volume":"53","author":"Nitulescu","year":"2018","journal-title":"Int. J. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.tcb.2006.03.008","article-title":"Apoptosis-inducing factor: Vital and lethal","volume":"16","author":"Modjtahedi","year":"2006","journal-title":"Trends Cell Biol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"L\u00fcersen, K., Stegehake, D., Daniel, J., Drescher, M., Ajonina, I., Ajonina, C., Hertel, P., Woltersdorf, C., and Liebau, E. (2013). The Glutathione Reductase GSR-1 Determines Stress Tolerance and Longevity in Caenorhabditis elegans. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060731"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1146\/annurev-pharmtox-011613-135959","article-title":"Targeting multidrug resistance protein 1 (MRP1, ABCC1): Past, present, and future","volume":"54","author":"Cole","year":"2014","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1096\/fj.05-3834fje","article-title":"T-cadherin protects endothelial cells from oxidative stress-induced apoptosis","volume":"19","author":"Joshi","year":"2005","journal-title":"FASEB J."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Williams, A.S., Kasahara, D.I., Verbout, N.G., Fedulov, A.V., Zhu, M., Si, H., Wurmbrand, A.P., Hug, C., Ranscht, B., and Shore, S.A. (2012). Role of the Adiponectin binding protein, T-cadherin (Cdh13), in allergic airways responses in mice. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041088"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/1742-2094-11-116","article-title":"The anti-inflammatory role of tissue inhibitor of metalloproteinase-2 in lipopolysaccharide-stimulated microglia","volume":"11","author":"Lee","year":"2014","journal-title":"J. Neuroinflamm."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"103236","DOI":"10.1016\/j.etap.2019.103236","article-title":"The role of ANXA5 in DBP-induced oxidative stress through ERK\/Nrf2 pathway","volume":"72","author":"Zhang","year":"2019","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1159\/000354513","article-title":"Factors Involved in Extracellular Matrix Turnover in Human Derived Cardiomyocytes","volume":"32","author":"Casals","year":"2013","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s12079-012-0180-4","article-title":"Anti-fibrotic effect of CCN3 accompanied by altered gene expression profile of the CCN family","volume":"7","author":"Kubota","year":"2013","journal-title":"J. Cell Commun. Signal."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7525","DOI":"10.1111\/jcmm.14621","article-title":"NOV\/CCN3 induces cartilage protection by inhibiting PI3K\/AKT\/mTOR pathway","volume":"23","author":"Huang","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s10529-018-2614-4","article-title":"COX6B1 relieves hypoxia\/reoxygenation injury of neonatal rat cardiomyocytes by regulating mitochondrial function","volume":"41","author":"Zhang","year":"2019","journal-title":"Biotechnol. Lett."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e004738","DOI":"10.1161\/JAHA.116.004738","article-title":"Cardiac overexpression of S100A6 attenuates cardiomyocyte apoptosis and reduces infarct size after myocardial ischemia-reperfusion","volume":"6","author":"Mofid","year":"2017","journal-title":"J. Am. Heart Assoc."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1093\/cvr\/cvr149","article-title":"Syndecan-4 signalling inhibits apoptosis and controls NFAT activity during myocardial damage and remodelling","volume":"92","author":"Echtermeyer","year":"2011","journal-title":"Cardiovasc. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3363","DOI":"10.1002\/jcb.24212","article-title":"Mesenchymal stem cell-derived interleukin-6 and vascular endothelial growth factor promote breast cancer cell migration","volume":"113","author":"Lamura","year":"2012","journal-title":"J. Cell Biochem."},{"key":"ref_62","first-page":"853","article-title":"SDC4 gene silencing favors human papillary thyroid carcinoma cell apoptosis and inhibits epithelial mesenchymal transition via wnt\/\u03b2-catenin pathway","volume":"41","author":"Chen","year":"2018","journal-title":"Mol. Cells"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s12935-014-0073-0","article-title":"Hsa-mir-30c promotes the invasive phenotype of metastatic breast cancer cells by targeting NOV\/CCN3","volume":"14","author":"Dobson","year":"2014","journal-title":"Cancer Cell Int."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Juurikka, K., Butler, G.S., Salo, T., Nyberg, P., and \u00c5str\u00f6m, P. (2019). The role of MMP8 in cancer: A systematic review. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184506"},{"key":"ref_65","first-page":"1116","article-title":"PDCD5 inhibits osteosarcoma cell metastasis via targeting tgf-\u03b21\/smad signaling pathway and is associated with good prognosis","volume":"11","author":"Zhao","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.bbcan.2016.10.002","article-title":"Guidelines for the selection of functional assays to evaluate the hallmarks of cancer","volume":"1866","author":"Sukumar","year":"2016","journal-title":"Biochim. Biophys. Acta-Rev. Cancer"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1111\/cbdd.12521","article-title":"Role of the Copper(II) Complex Cu[15]pyN5 in Intracellular ROS and Breast Cancer Cell Motility and Invasion","volume":"86","author":"Fernandes","year":"2015","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_68","unstructured":"Santos, J.M., Soares, R., Coelho, M., Martins, J.P., Basto, V., Cruz, P., and Cruz, H. (2021, March 08). Optimised and Defined Method for Isolation and Preservation of Percursor Cells from Human Umbilical Cord. Available online: https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=WO2009044379."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/scrt398","article-title":"Towards an advanced therapy medicinal product based on mesenchymal stromal cells isolated from the umbilical cord tissue: Quality and safety data","volume":"5","author":"Martins","year":"2014","journal-title":"Stem Cell Res. Ther."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"D442","DOI":"10.1093\/nar\/gky1106","article-title":"The PRIDE database and related tools and resources in 2019: Improving support for quantification data","volume":"47","author":"Csordas","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: A comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1007\/s00436-005-0105-8","article-title":"Development of a recombinant indirect ELISA for the diagnosis of Theileria sp. (China) infection in small ruminants","volume":"98","author":"Miranda","year":"2006","journal-title":"Parasitol. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/23\/13072\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:39:09Z","timestamp":1760168349000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/23\/13072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,3]]},"references-count":73,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["ijms222313072"],"URL":"https:\/\/doi.org\/10.3390\/ijms222313072","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2021,12,3]]}}}