{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T06:43:38Z","timestamp":1762325018227,"version":"build-2065373602"},"reference-count":88,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,5,9]],"date-time":"2021-05-09T00:00:00Z","timestamp":1620518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Amparo a Pesquisa do Estado de Sao Paulo","award":["2012\/17120-6 and 2015\/21068-8"],"award-info":[{"award-number":["2012\/17120-6 and 2015\/21068-8"]}]},{"name":"UNM Comprehensive Cancer Center Support Grant","award":["NCI P30CA118100"],"award-info":[{"award-number":["NCI P30CA118100"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The role and prognostic value of tetraspanins (TSPANs) in vulvar squamous cell carcinoma (VSCC) remain poorly understood. We sought to primarily determine, at both the molecular and tissue level, the expression profile of the TSPANs CD9, CD63, CD81, and CD82 in archived VSCC samples (n = 117) and further investigate their clinical relevance as prognostic markers. Our studies led us to identify CD63 as the most highly expressed TSPAN, at the gene and protein levels. Multicomparison studies also revealed that the expression of CD9 was associated with tumor size, whereas CD63 upregulation was associated with histological diagnosis and vascular invasion. Moreover, low expression of CD81 and CD82 was associated with worse prognosis. To determine the role of TSPANs in VSCC at the cellular level, we assessed the mRNA levels of CD63 and CD82 in established metastatic (SW962) and non-metastatic (SW954) VSCC human cell lines. CD82 was found to be downregulated in SW962 cells, thus supporting its metastasis suppressor role. However, CD63 was significantly upregulated in both cell lines. Silencing of CD63 by siRNA led to a significant decrease in proliferation of both SW954 and SW962. Furthermore, in SW962 particularly, CD63-siRNA also remarkably inhibited cell migration. Altogether, our data suggest that the differential expression of TSPANs represents an important feature for prognosis of VSCC patients and indicates that CD63 and CD82 are likely potential therapeutic targets in VSCC.<\/jats:p>","DOI":"10.3390\/ijms22095015","type":"journal-article","created":{"date-parts":[[2021,5,9]],"date-time":"2021-05-09T21:32:46Z","timestamp":1620595966000},"page":"5015","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Assessment of TSPAN Expression Profile and Their Role in the VSCC Prognosis"],"prefix":"10.3390","volume":"22","author":[{"given":"Kelly Pedrozo","family":"Ferreira","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Ginecologia Estrutural e Molecular (LIM 58), Disciplina de Ginecologia, Departamento de Obstetricia e Ginecologia, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, HCFMUSP, SP, BR Av. Dr Arnaldo 455, sala 4121, Cerqueira Cesar, S\u00e3o Paulo 05403-010, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1641-5609","authenticated-orcid":false,"given":"Bruna Cristine","family":"de Almeida","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ginecologia Estrutural e Molecular (LIM 58), Disciplina de Ginecologia, Departamento de Obstetricia e Ginecologia, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, HCFMUSP, SP, BR Av. Dr Arnaldo 455, sala 4121, Cerqueira Cesar, S\u00e3o Paulo 05403-010, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9027-8281","authenticated-orcid":false,"given":"Laura Gonzalez","family":"dos Anjos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ginecologia Estrutural e Molecular (LIM 58), Disciplina de Ginecologia, Departamento de Obstetricia e Ginecologia, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, HCFMUSP, SP, BR Av. Dr Arnaldo 455, sala 4121, Cerqueira Cesar, S\u00e3o Paulo 05403-010, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glauco","family":"Baiocchi","sequence":"additional","affiliation":[{"name":"Department of Gynecology Oncology, A. C. Camargo Cancer Center, Rua Prof Antonio Prudente 211, S\u00e3o Paulo 01509-001, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando Augusto","family":"Soares","sequence":"additional","affiliation":[{"name":"Department of Pathology, Rede D\u2019OR-S\u00e3o Luiz, Rua das Perobas, 344-Jabaquara, S\u00e3o Paulo 04321-120, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael Malagoli","family":"Rocha","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Federal University of S\u00e3o Paulo (UNIFESP), R. Napole\u00e3o de Barros, 608, Vila Clementino, S\u00e3o Paulo 04024-002, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edmund Chada","family":"Baracat","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ginecologia Estrutural e Molecular (LIM 58), Disciplina de Ginecologia, Departamento de Obstetricia e Ginecologia, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, HCFMUSP, SP, BR Av. Dr Arnaldo 455, sala 4121, Cerqueira Cesar, S\u00e3o Paulo 05403-010, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2162-9951","authenticated-orcid":false,"given":"Andrey Senos","family":"Dobroff","sequence":"additional","affiliation":[{"name":"University of New Mexico Comprehensive Cancer Center (UNMCCC), 1 University of New Mexico, Albuquerque, NM 87131, USA"},{"name":"Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico (UNM) School of Medicine, UNM Health Sciences Center, 1 University of New Mexico, MSC07 4025, Cancer Research Facility (CRF) 321A, Albuquerque, NM 87131, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7295-678X","authenticated-orcid":false,"given":"Katia Candido","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ginecologia Estrutural e Molecular (LIM 58), Disciplina de Ginecologia, Departamento de Obstetricia e Ginecologia, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, HCFMUSP, SP, BR Av. Dr Arnaldo 455, sala 4121, Cerqueira Cesar, S\u00e3o Paulo 05403-010, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1007\/s00432-020-03226-6","article-title":"Molecular pathways in vulvar squamous cell carcinoma: Implications for target therapeutic strategies","volume":"146","author":"Giulia","year":"2020","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_2","unstructured":"(2020, July 13). American Cancer Society Home-Cancer Statistics Center. Available online: https:\/\/cancerstatisticscenter.cancer.org\/#!\/."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1080\/01443615.2017.1318269","article-title":"Cutaneous metastasis from vulvar squamous cell carcinoma: A rare occurrence that should not be forgotten","volume":"37","author":"Bizzarri","year":"2017","journal-title":"J. Obstet. Gynaecol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/ijgo.12609","article-title":"Cancer of the vulva","volume":"143","author":"Rogers","year":"2018","journal-title":"Int. J. Gynecol. Obstet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1136\/ijgc-2019-000793","article-title":"Association of human papilloma virus status and response to radiotherapy in vulvar squamous cell carcinoma","volume":"30","author":"Proctor","year":"2020","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1002\/ijc.31139","article-title":"Does HPV status influence survival after vulvar cancer?","volume":"142","author":"Rasmussen","year":"2018","journal-title":"Int. J. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.ygyno.2017.11.006","article-title":"Prognostic factors for local recurrence of squamous cell carcinoma of the vulva: A systematic review","volume":"148","author":"Pouwer","year":"2018","journal-title":"Gynecol. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1097\/PAS.0000000000001540","article-title":"HPV-independent precursors mimicking high-grade squamous intraepithelial lesions (HSIL) of the vulva","volume":"44","author":"Rakislova","year":"2020","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.ejso.2013.03.004","article-title":"Prognostic value of the number and laterality of metastatic inguinal lymph nodes in vulvar cancer: Revisiting the FIGO staging system","volume":"39","author":"Baiocchi","year":"2013","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1016\/j.ejso.2015.09.024","article-title":"How important is the pathological margin distance in vulvar cancer?","volume":"41","author":"Baiocchi","year":"2015","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1097\/GCO.0000000000000595","article-title":"New treatment standards for vulvar cancer 2020","volume":"32","author":"Woelber","year":"2020","journal-title":"Curr. Opin. Obstet. Gynecol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1055\/s-0032-1328133","article-title":"Use of the sentinel lymph node technique compared to complete inguino-femoral lymph node removal in patients with invasive vulvar cancer in Germany","volume":"73","author":"Kramer","year":"2013","journal-title":"Geburtshilfe Frauenheilkd."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.ygyno.2017.05.011","article-title":"Identification of molecular targets in vulvar cancers","volume":"146","author":"Palisoul","year":"2017","journal-title":"Gynecol. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"49217","DOI":"10.18632\/oncotarget.10247","article-title":"MiR-223-5p works as an oncomiR in vulvar carcinoma by TP63 suppression","volume":"7","author":"Maia","year":"2016","journal-title":"Oncotarget"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3713","DOI":"10.1007\/s13277-013-0955-0","article-title":"Cell cycle suppressor proteins are not related to HPV status or clinical outcome in patients with vulvar carcinoma","volume":"34","author":"Rodrigues","year":"2013","journal-title":"Tumor. Biol."},{"key":"ref_16","first-page":"508","article-title":"Molecular characterization of invasive and in situ squamous neoplasia of the vulva and implications for morphologic diagnosis and outcome","volume":"34","author":"Pors","year":"2020","journal-title":"Mod. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"978","DOI":"10.4049\/jimmunol.1500357","article-title":"Dendritic cell migration and antigen presentation are coordinated by the opposing functions of the tetraspanins CD82 and CD37","volume":"196","author":"Jones","year":"2016","journal-title":"J. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/nrm1736","article-title":"Tetraspanin functions and associated microdomains","volume":"6","author":"Hemler","year":"2005","journal-title":"Nat. Rev. Molecul. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3389\/fcell.2017.00034","article-title":"Tetraspanins function as regulators of cellular signaling","volume":"5","author":"Termini","year":"2017","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.cub.2020.01.007","article-title":"Tetraspanins","volume":"30","author":"Lang","year":"2020","journal-title":"Curr. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s10238-019-00554-x","article-title":"Expression of tetraspanins NET-6 and CD151 in breast cancer as a potential tumor biomarker","volume":"19","author":"Jiang","year":"2019","journal-title":"Clin. Exp. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.drudis.2020.10.022","article-title":"Tetraspanins: Useful multifunction proteins for the possible design and development of small-molecule therapeutic tools","volume":"26","author":"Robert","year":"2020","journal-title":"Drug Discov. Today"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.micinf.2009.11.001","article-title":"The role of tetraspanins in the pathogenesis of infectious diseases","volume":"12","author":"Figdor","year":"2010","journal-title":"Microbes Infect."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s00428-008-0590-0","article-title":"Down-regulation of the metastasis suppressor protein KAI1\/CD82 correlates with occurrence of metastasis, prognosis and presence of HPV DNA in human penile squamous cell carcinoma","volume":"452","author":"Protzel","year":"2008","journal-title":"Virchows Arch."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Spoden, G., Freitag, K., Husmann, M., Boller, K., Sapp, M., Lambert, C., and Florin, L. (2008). Clathrin- and caveolin-independent entry of human papillomavirus type 16-Involvement of tetraspanin-enriched microdomains (TEMs). PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003313"},{"key":"ref_26","first-page":"85","article-title":"The roles of tetraspanins in HIV-1 replication","volume":"339","author":"Thali","year":"2009","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1042\/BST0390529","article-title":"Tetraspanin functions during HIV-1 and influenza virus replication","volume":"39","author":"Thali","year":"2011","journal-title":"Biochem. Soc. Trans."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Fast, L.A., Mikuli\u010di\u0107, S., Fritzen, A., Schwickert, J., Boukhallouk, F., Hochdorfer, D., Sinzger, C., Suarez, H., Monk, P.N., and Y\u00e1\u00f1ez-M\u00f3, M. (2018). Inhibition of tetraspanin functions impairs human papillomavirus and cytomegalovirus infections. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19103007"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Earnest, J.T., Hantak, M.P., Li, K., McCray, P.B., Perlman, S., and Gallagher, T. (2017). The tetraspanin CD9 facilitates MERS-coronavirus entry by scaffolding host cell receptors and proteases. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006546"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e01429-17","DOI":"10.1128\/JVI.01429-17","article-title":"Tetraspanins: Architects of viral entry and exit platforms","volume":"93","author":"Hantak","year":"2019","journal-title":"J. Virol."},{"key":"ref_31","first-page":"887","article-title":"Tetraspanin CD63 independently predicts poor prognosis in colorectal cancer","volume":"35","author":"Kaprio","year":"2020","journal-title":"Histol. Histopathol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ridnour, L.A., Barasch, K.M., Windhausen, A.N., Dorsey, T.H., Lizardo, M.M., Yfantis, H.G., Lee, D.H., Switzer, C.H., Cheng, R.Y.S., and Heinecke, J.L. (2012). Nitric Oxide Synthase and breast cancer: Role of TIMP-1 in NO-mediated Akt activation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044081"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4540","DOI":"10.1038\/onc.2015.520","article-title":"Therapeutic targeting of tetraspanin8 in epithelial ovarian cancer invasion and metastasis","volume":"35","author":"Park","year":"2016","journal-title":"Oncogene"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"111622","DOI":"10.1016\/j.yexcr.2019.111622","article-title":"Tspan15 plays a crucial role in metastasis in oral squamous cell carcinoma","volume":"384","author":"Hiroshima","year":"2019","journal-title":"Exp. Cell Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"737","DOI":"10.3892\/or.2016.4893","article-title":"p12CDK2-AP1 interacts with CD82 to regulate the proliferation and survival of human oral squamous cell carcinoma cells","volume":"36","author":"Chai","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_36","first-page":"3054","article-title":"Overexpression of CD9 correlates with tumor stage and lymph node metastasis in esophageal squamous cell carcinoma","volume":"8","author":"Huan","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_37","first-page":"5928","article-title":"CD82\/KAI1 inhibits invasion and metastasis of esophageal squamous cell carcinoma via TGF-\u03b21","volume":"22","author":"Zeng","year":"2018","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.exphem.2016.02.006","article-title":"Tetraspanins: Spanning from solid tumors to hematologic malignancies","volume":"44","author":"Yang","year":"2016","journal-title":"Exp. Hematol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Heo, K., and Lee, S. (2020). TSPAN8 as a novel emerging therapeutic target in cancer for monoclonal antibody therapy. Biomolecules, 10.","DOI":"10.3390\/biom10030388"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1016\/j.yexcr.2008.09.020","article-title":"Trafficking and function of the tetraspanin CD63","volume":"315","author":"Pols","year":"2009","journal-title":"Exp. Cell Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3851","DOI":"10.1096\/fj.201800664RR","article-title":"Cell surface CD63 increased by up-regulated polylactosamine modification sensitizes human melanoma cells to the BRAF inhibitor PLX4032","volume":"33","author":"Kudo","year":"2019","journal-title":"FASEB J."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Garcia-Mayea, Y., Mir, C., Carballo, L., Castellvi, J., Temprana-Salvador, J., Lorente, J., Benavente, S., Garc\u00eda-Pedrero, J.M., Allonca, E., and Rodrigo, J.P. (2020). TSPAN1: A Novel Protein Involved in Head and Neck Squamous Cell Carcinoma Chemoresistance. Cancers (Basel), 12.","DOI":"10.3390\/cancers12113269"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1111\/1759-7714.13492","article-title":"Prognostic role of extracellular vesicles in squamous cell carcinoma of the lung","volume":"11","author":"An","year":"2020","journal-title":"Thorac. Cancer"},{"key":"ref_44","first-page":"31","article-title":"Prognostication of vulvar cancer based on p14ARF status: Molecular assessment of transcript and protein","volume":"20","author":"Maia","year":"2012","journal-title":"Ann. Surg. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Akagi, E.M., Lavorato-Rocha, A.M., Maia, B.M., Rodrigues, I.S., Carvalho, K.C., Stiepcich, M.M., Baiocchi, G., Sato-Kuwabara, Y., Rogatto, S.R., and Soares, F.A. (2014). ROCK1 as a novel prognostic marker in vulvar cancer. BMC Cancer, 14.","DOI":"10.1186\/1471-2407-14-822"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.humpath.2014.01.015","article-title":"EGFR expression in vulvar cancer: Clinical implications and tumor heterogeneity","volume":"45","author":"Maia","year":"2014","journal-title":"Hum. Pathol."},{"key":"ref_47","first-page":"20","article-title":"Immunohistochemical assessment of PTEN in vulvar cancer: Best practices for tissue staining, evaluation, and clinical association","volume":"77","author":"Anjos","year":"2015","journal-title":"Methods"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1158\/1541-7786.MCR-15-0366","article-title":"An integrative approach uncovers biomarkers that associate with clinically relevant disease outcomes in vulvar carcinoma","volume":"14","author":"Akagi","year":"2016","journal-title":"Mol. Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/1479-5876-10-150","article-title":"Prognostic significance of c-KIT in vulvar cancer: Bringing this molecular marker from bench to bedside","volume":"10","author":"Maia","year":"2012","journal-title":"J. Transl. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1159\/000343758","article-title":"Characterization of sociodemographic and clinicopathological features in brazilian patients with vulvar squamous cell carcinoma","volume":"75","author":"Maia","year":"2013","journal-title":"Gynecol. Obst. Investig."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.ejso.2013.02.012","article-title":"Does the count after inguinofemoral lymphadenectomy in vulvar cancer correlate with outcome?","volume":"39","author":"Baiocchi","year":"2013","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_52","first-page":"37","article-title":"A review of prognostic factors in squamous cell carcinoma of the vulva: Evidence from the last decade","volume":"38","author":"Chen","year":"2020","journal-title":"Semin. Diagn. Pathol."},{"key":"ref_53","first-page":"1045","article-title":"MRP-1\/CD9 and KAI1\/CD82 expression in normal and various cancer tissues","volume":"11","author":"Huang","year":"1997","journal-title":"Int. J. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"77","DOI":"10.4048\/jbc.2019.22.e9","article-title":"CD9 expression in tumor cells is associated with poor prognosis in patients with invasive lobular carcinoma","volume":"22","author":"Baek","year":"2019","journal-title":"J. Breast Cancer"},{"key":"ref_55","first-page":"1244","article-title":"Motility-related Protein-1 (MRP-1\/CD9) reduction as a factor of poor prognosis in breast cancer","volume":"56","author":"Miyake","year":"1996","journal-title":"Cancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S0002-9440(10)65639-8","article-title":"Correlation of reduction in MRP-1\/CD9 and KAI1\/CD82 expression with recurrences in breast cancer patients","volume":"153","author":"Huang","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1038\/sj.bjc.6690186","article-title":"Motility-related protein (MRP-1\/CD9) and KAI1\/CD82 expression inversely correlate with lymph node metastasis in oesophageal squamous cell carcinoma","volume":"79","author":"Uchida","year":"1999","journal-title":"Br. J. Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1034\/j.1600-0714.2001.300202.x","article-title":"Reduced expression of CD9 in oral squamous cell carcinoma: CD9 expression inversely related to high prevalence of lymph node metastasis","volume":"30","author":"Kusukawa","year":"2001","journal-title":"J. Oral. Pathol. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.oraloncology.2009.11.009","article-title":"Downregulation of CD9 protein expression is associated with aggressive behavior of oral squamous cell carcinoma","volume":"46","author":"Buim","year":"2010","journal-title":"Oral. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.jss.2004.01.014","article-title":"CD9 expression in gastric cancer and its significance","volume":"117","author":"Hori","year":"2004","journal-title":"J. Surg. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.prp.2010.04.004","article-title":"Prognostic significance of CD9 expression in locally advanced gastric cancer treated with surgery and adjuvant chemoradiotherapy","volume":"206","author":"Soyuer","year":"2010","journal-title":"Pathol. Res. Pract."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.prp.2014.01.004","article-title":"Expression of CD9 and CD82 in clear cell renal cell carcinoma and its clinical significance","volume":"210","author":"Kwon","year":"2014","journal-title":"Pathol. Res. Pract."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1002\/(SICI)1097-0215(19981023)79:5<509::AID-IJC11>3.0.CO;2-X","article-title":"Transmembrane 4 superfamily as a prognostic factor in pancreatic cancer","volume":"79","author":"Sho","year":"1998","journal-title":"Int. J. Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"9557","DOI":"10.1158\/0008-5472.CAN-06-1131","article-title":"Absence of CD9 enhances adhesion-dependent morphologic differentiation, survival, and matrix metalloproteinase-2 production in small cell lung cancer cells","volume":"66","author":"Saito","year":"2006","journal-title":"Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1084\/jem.177.5.1231","article-title":"Suppression of cell motility and metastasis by transfection with human motility-related protein (MRP-1\/CD9) DNA","volume":"177","author":"Ikeyama","year":"1993","journal-title":"J. Exp. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"24279","DOI":"10.1074\/jbc.M601209200","article-title":"Homophilic interactions of tetraspanin CD151 up-regulate motility and matrix metalloproteinase-9 expression of human melanoma cells through adhesion-dependent c-Jun activation signaling pathways","volume":"281","author":"Hong","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_67","unstructured":"Guidone, L.R.M. (2010). Imunoexpress\u00e3o CD9 No Carcinoma Epiderm\u00f3ide Do P\u00eanis. [Master\u2019s Thesis, (MsC) FAP-Hospital A C Camargo]."},{"key":"ref_68","first-page":"2665","article-title":"EWI2\/PGRL Associates with the Metastasis SuppressorSS KAI1\/CD82 and Inhibits the Migration of Prostate Cancer Cells","volume":"63","author":"Zhang","year":"2003","journal-title":"Cancer Res."},{"key":"ref_69","first-page":"519","article-title":"KAI-1\/CD82, the molecule and clinical implication in cancer and cancer metastasis","volume":"24","author":"Malik","year":"2009","journal-title":"Histol. Histopathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1186\/s12957-017-1279-0","article-title":"Roles of KAI1 and nm23 in lymphangiogenesis and lymph metastasis of laryngeal squamous cell carcinoma","volume":"15","author":"Zheng","year":"2017","journal-title":"World J. Surg. Oncol."},{"key":"ref_71","first-page":"5284","article-title":"Overexpression of KAI1 Suppresses in vitro invasiveness and in vivo metastasis in breast cancer cells","volume":"61","author":"Yang","year":"2001","journal-title":"Cancer Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.31557\/APJCP.2020.21.9.2549","article-title":"Investigations of a possible role of SNPs in KAI1 gene on its down-regulation in breast cancer","volume":"21","author":"Kussaibi","year":"2020","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.bbrc.2006.01.153","article-title":"KAI1\/CD82 suppresses tumor invasion by MMP9 inactivation via TIMP1 up-regulation in the H1299 human lung carcinoma cell line","volume":"342","author":"Jee","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.3892\/mmr.2017.6186","article-title":"Overexpression of KAI1\/CD82 suppresses in vitro cell growth, migration, invasion and xenograft growth in oral cancer","volume":"15","author":"Chai","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"8899924","DOI":"10.1155\/2020\/8899924","article-title":"CD82 Suppresses ADAM17-Dependent E-Cadherin cleavage and cell migration in prostate cancer","volume":"2020","author":"Ma","year":"2020","journal-title":"Dis. Markers"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1080\/19336918.2020.1732761","article-title":"EpCAM-claudin-tetraspanin-modulated ovarian cancer progression and drug resistance","volume":"14","author":"Tavsan","year":"2020","journal-title":"Cell Adh. Migr."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1007\/s13402-019-00472-w","article-title":"The tetraspanin CD81 mediates the growth and metastases of human osteosarcoma","volume":"42","author":"Mizoshiri","year":"2019","journal-title":"Cell Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1042\/BST20160478","article-title":"CD81 as a tumor target","volume":"45","author":"Duault","year":"2017","journal-title":"Biochem. Soc. Trans."},{"key":"ref_79","first-page":"1719","article-title":"Proteomics profiling of plasma exosomes in epithelial ovarian cancer: A potential role in the coagulation cascade, diagnosis and prognosis","volume":"54","author":"Zhang","year":"2019","journal-title":"Int. J. Oncol."},{"key":"ref_80","first-page":"755","article-title":"Increased expression of CD81 is associated with poor prognosis of prostate cancer and increases the progression of prostate cancer cells in vitro","volume":"19","author":"Zhang","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2649","DOI":"10.1038\/onc.2012.268","article-title":"Cell fusion promotes chemoresistance in metastatic colon carcinoma","volume":"32","author":"Carloni","year":"2013","journal-title":"Oncogene"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4393","DOI":"10.1182\/bloodadvances.2020001592","article-title":"CD81 knockout promotes chemosensitivity and disrupts in vivo homing and engraftment in acute lymphoblastic leukemia","volume":"4","author":"Quagliano","year":"2020","journal-title":"Blood Adv."},{"key":"ref_83","unstructured":"(2018, October 19). American Type Culture Collection Search ATCC STR Database. Available online: https:\/\/www.atcc.org\/STR_Database.aspx."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"5245","DOI":"10.1158\/0008-5472.CAN-04-0496","article-title":"Normalization of real-time quantitative reverse transcription-PCR data: A model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets","volume":"64","author":"Andersen","year":"2004","journal-title":"Cancer Res."},{"key":"ref_85","first-page":"1024","article-title":"Tetraspanin expression profile in soft tissue sarcomas","volume":"2","author":"Carvalho","year":"2015","journal-title":"J. Dis. Markers"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/bjc.2013.273","article-title":"Epithelial-mesenchymal transition-like events in vulvar cancer and its relation with HPV","volume":"109","author":"Rodrigues","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"De Almeida, B.C., dos Anjos, L.G., Uno, M., Cunha, I.W., Soares, F.A., Baiocchi, G., Baracat, E.C., and Carvalho, K.C. (2019). Let-7 miRNA\u2019s expression profile and its potential prognostic role in uterine leiomyosarcoma. Cells, 8.","DOI":"10.3390\/cells8111452"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Kumari, S., Nie, J., Chen, H.-S., Ma, H., Stewart, R., Li, X., Lu, M.-Z., Taylor, W.M., and Wei, H. (2012). Evaluation of gene association methods for coexpression network construction and biological knowledge discovery. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0050411"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/9\/5015\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:58:26Z","timestamp":1760162306000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/9\/5015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,9]]},"references-count":88,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["ijms22095015"],"URL":"https:\/\/doi.org\/10.3390\/ijms22095015","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2021,5,9]]}}}