Assessment of TSPAN Expression Profile and Their Role in the VSCC Prognosis

Author(s)

Ferreira, Kelly Pedrozo ^[1] ; de Almeida, Bruna Cristine ^[1] ; dos Anjos, Laura Gonzalez ^[1] ; Baiocchi, Glauco ^[2] ; Soares, Fernando Augusto ^[3] ; Rocha, Rafael Malagoli ^[4] ; Baracat, Edmund Chada ^[1] ; Dobroff, Andrey Senos ^[5] ; Carvalho, Katia Candido ^{[1, 6]}

Affiliation

^[1] Univ Sao Paulo, HCFMUSP, Fac Med, Hosp Clin, Lab Ginecol Estrutural & Mol LIM 58, Dept Obstetri, BR Ave Dr Arnaldo 455, Sala 4121, BR-05403010 Sao Paulo - Brazil

^[2] AC Camargo Canc Ctr, Dept Gynecol Oncol, Rua Prof Antonio Prudente 211, BR-01509001 Sao Paulo - Brazil

^[3] Rede DOR Sao Luiz, Dept Pathol, Rua Perobas, 344-Jabaquara, BR-04321120 Sao Paulo - Brazil

^[4] Fed Univ Sao Paulo UNIFESP, Dept Gynecol, R Napoleao Barros, 608, Vila Clementino, BR-04024002 Sao Paulo - Brazil

^[5] 1 Univ New Mexico, Comprehens Canc Ctr UNMCCC, Albuquerque, NM 87131 - USA

^[6] 1 Univ New Mexico, Sch Med, UNM Hlth Sci Ctr, Div Mol Med, Dept Internal Med, MSC07 4025, Canc Res Facility CRF 321A, Albuquerque, NM 87131 - USA

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 9 MAY 2021.
• Web of Science Citations: 0

Abstract

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. (AU)

• FAPESP's process: 12/17120-6 - Tetraspanins in vulvar carcinoma: correlation of CD9, CD63, CD81 and CD82 with HPV infection and prognosis
• Grantee: Kátia Cândido Carvalho
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/21068-8 - In vivo and in vitro functional validation of the Sonic Hedgehog signaling pathway inhibitors in uterine leiomyoma and leiomyosarcoma
• Grantee: Kátia Cândido Carvalho
• Support Opportunities: Regular Research Grants