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TSPAN 表达谱评估及其在 VSCC 预后中的作用。

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

机构信息

Laboratório 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, São Paulo 05403-010, Brazil.

Department of Gynecology Oncology, A. C. Camargo Cancer Center, Rua Prof Antonio Prudente 211, São Paulo 01509-001, Brazil.

出版信息

Int J Mol Sci. 2021 May 9;22(9):5015. doi: 10.3390/ijms22095015.

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 ( = 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. was found to be downregulated in SW962 cells, thus supporting its metastasis suppressor role. However, 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, 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.

摘要

四跨膜蛋白(TSPANs)在外阴鳞状细胞癌(VSCC)中的作用和预后价值仍知之甚少。我们主要旨在确定 TSPANs CD9、CD63、CD81 和 CD82 在存档的 VSCC 样本(= 117)中的分子和组织水平上的表达谱,并进一步研究它们作为预后标志物的临床相关性。我们的研究表明,CD63 在基因和蛋白水平上的表达最高。多比较研究还表明,CD9 的表达与肿瘤大小有关,而 CD63 的上调与组织学诊断和血管浸润有关。此外,CD81 和 CD82 的低表达与预后不良有关。为了确定 TSPANs 在 VSCC 中的细胞水平作用,我们评估了在建立的转移性(SW962)和非转移性(SW954)VSCC 人细胞系中 CD63 和 CD82 的 mRNA 水平。发现 SW962 细胞中的 表达下调,从而支持其作为转移抑制因子的作用。然而,在这两种细胞系中,均显著上调。通过 siRNA 沉默 CD63 导致 SW954 和 SW962 细胞增殖显著减少。此外,特别是在 SW962 中,还显著抑制了细胞迁移。总的来说,我们的数据表明 TSPANs 的差异表达代表了 VSCC 患者预后的一个重要特征,并表明 CD63 和 CD82 可能是 VSCC 的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddce/8125994/05a561e8c999/ijms-22-05015-g001.jpg

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