四跨膜蛋白(TSPANs)在外阴鳞状细胞癌(VSCC)中的作用和预后价值尚不清楚。我们试图首先确定,在分子和组织水平上,在存档的VSCC样本(n=117)中TSPANsCD9,CD63,CD81和CD82的表达谱,并进一步研究其作为预后标志物的临床相关性.我们的研究使我们确定CD63是表达最高的TSPAN,在基因和蛋白质水平。多重比较研究还显示CD9的表达与肿瘤大小有关。而CD63上调与组织学诊断和血管侵犯有关。此外,CD81和CD82的低表达与预后较差相关.为了在细胞水平上确定TSPAN在VSCC中的作用,我们评估了已建立的转移性(SW962)和非转移性(SW954)VSCC人细胞系中CD63和CD82的mRNA水平。CD82在SW962细胞中被下调,从而支持其转移抑制作用。然而,CD63在两种细胞系中均显著上调。通过siRNA使CD63沉默导致SW954和SW962两者的增殖显著降低。此外,特别是在SW962中,CD63-siRNA也显著抑制细胞迁移。总之,我们的数据提示TSPAN的差异表达是VSCC患者预后的重要特征,并提示CD63和CD82可能是VSCC的潜在治疗靶点.
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.