文章：

四联蛋白促进多种癌症分期

Tetraspanin proteins promote multiple cancer stages

原文发布日期：2013-12-23

DOI: 10.1038/nrc3640

类型: Review Article

开放获取: 否

要点：

1. New evidence from in vivo mouse models confirms that tetraspanin proteins can contribute substantially to tumour initiation, promotion and progression.
2. In vivo evidence also shows that the tetraspanin CD151 makes substantial contributions to metastasis, and tetraspanin 8 (TSPAN8) can also contribute to metastasis.
3. Although the tetraspanin CD9 is primarily known as a tumour suppressor, it sometimes has oncogenic and pro-metastatic functions. The association of CD9 with different partner proteins could explain its diverse functions.
4. A few tetraspanins (including CD151, TSPAN8 and CD9) contribute to tumour angiogenesis, presumably by affecting endothelial cell function. However, the contributions of tetraspanins to angiogenesis have not yet been shown using de novo tumour models.
5. Intact and modified CD37-specific monoclonal antibodies have shown considerable promise in the treatment of B cell malignancies. These reagents can kill malignant B cells by inducing antibody-dependent cell-mediated cytotoxicity, by delivering lethal radiation and by inducing apoptosis.
6. CD151-specific monoclonal antibodies have been developed that can strongly inhibit both metastasis and primary tumour growth in human–mouse xenograft models.
7. Other tetraspanins (TSPAN8, CD9 and TSPAN12) may also be worthy cancer targets in particular circumstances.
8. The targeting of CD151 (and perhaps CD9 and CD81) might increase cancer cell sensitivity to several other types of anticancer drugs.

要点翻译：

1. 来自小鼠体内模型的新证据证实，四跨膜蛋白对肿瘤的发生、促进和进展具有重要贡献。
2. 体内证据还表明，四跨膜蛋白CD151对转移有显著影响，而四跨膜蛋白8（TSPAN8）也可能促进转移。
3. 虽然四跨膜蛋白CD9主要被认为是一种肿瘤抑制因子，但有时它也具有致癌和促转移功能。CD9与不同伴侣蛋白的结合可能解释其多样化的功能。
4. 一些四跨膜蛋白（包括CD151、TSPAN8和CD9）通过影响内皮细胞功能参与肿瘤血管生成。然而，四跨膜蛋白对血管生成的贡献尚未通过新生肿瘤模型得到证实。
5. 完整和修饰后的CD37特异性单克隆抗体在治疗B细胞恶性肿瘤中显示出巨大潜力。这些试剂可通过诱导抗体依赖性细胞介导的细胞毒性、传递致死辐射以及诱导凋亡来杀死恶性B细胞。
6. 已开发出CD151特异性单克隆抗体，在人类-小鼠异种移植模型中能够强烈抑制转移和原发性肿瘤生长。
7. 其他四跨膜蛋白（TSPAN8、CD9和TSPAN12）在特定情况下也可能成为有价值的癌症靶点。
8. 靶向CD151（可能还包括CD9和CD81）可能会增加癌细胞对其他几种抗癌药物的敏感性。

英文摘要：

An abundance of evidence shows supporting roles for tetraspanin proteins in human cancer. Many studies show that the expression of tetraspanins correlates with tumour stage, tumour type and patient outcome. In addition, perturbations of tetraspanins in tumour cell lines can considerably affect cell growth, morphology, invasion, tumour engraftment and metastasis. This Review emphasizes new studies that have used de novo mouse cancer models to show that select tetraspanin proteins have key roles in tumour initiation, promotion and metastasis. This Review also emphasizes how tetraspanin proteins can sometimes participate in tumour angiogenesis. These recent data build an increasingly strong case for tetraspanins as therapeutic targets.

摘要翻译： 

大量证据表明，四跨膜蛋白（tetraspanin）在癌症中发挥支持作用。许多研究显示，四跨膜蛋白的表达与肿瘤分期、类型及患者预后相关。此外，在肿瘤细胞系中干扰四跨膜蛋白可显著影响细胞生长、形态、侵袭、肿瘤接种和转移。本综述重点介绍了利用新生小鼠癌症模型的最新研究，证实特定四跨膜蛋白在肿瘤起始、促进和转移中起关键作用。同时，本文也强调了四跨膜蛋白有时参与肿瘤血管生成的机制。这些最新数据进一步巩固了四跨膜蛋白作为治疗靶点的有力依据。

原文链接：

Tetraspanin proteins promote multiple cancer stages