Tetraspanin CD151 as a target for antibody-based cancer immunotherapy
Tetraspanin CD151 as a target for antibody-based cancer immunotherapy
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DOI：
10.1042/bst0390553
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发表时间：
2011-04-01
影响因子：
3.9
通讯作者：
Corvaia, Nathalie
中科院分区：
文献类型：
--
作者：
Haeuw, Jean-Francois;Goetsch, Liliane;Corvaia, Nathalie
CD151是一种质膜蛋白，属于四跨膜蛋白超家族，它在正常细胞如内皮细胞和血小板上表达，并且在癌细胞上经常过度表达。已知它在功能上与癌症转移相关。在人类中，CD151表达增加预示着不同癌症类型的预后不良。尽管其作用机制仍不清楚，但已表明CD151通过与层粘连蛋白结合整合素（如α3β1或α6β4）相关联来调节细胞运动和黏附。几种抗CD151单克隆抗体（mAbs）已被证明在体内具有抗转移活性。转移的抑制并非归因于这些mAbs对肿瘤细胞生长的任何影响，而主要归因于对细胞运动的抑制。我们已经制备了抗CD151 mAbs，它们能够抑制不同异种移植癌症模型中的肿瘤生长。正如预期的那样，这些mAbs也能够抑制原位癌症模型中的转移。这些数据表明CD151可以在癌症的多个阶段发挥作用，不仅包括转移级联步骤，还包括原发性肿瘤生长的早期步骤，从而增强了这个创新靶点在肿瘤学中的研究价值。靶向CD151的mAbs可能对癌症生物治疗具有重要意义。
CD151 is a plasma membrane protein belonging to the tetraspanin superfamily which is expressed on normal cells such as endothelial cells and platelets and frequently overexpressed on cancer cells. It is known to be functionally linked to cancer metastasis. In humans, increased expression of CD151 is indicative of a poor prognosis in different cancer types. Whereas its mechanism of action remains obscure, CD151 was shown to regulate cell motility and adhesion through association with laminin-binding integrins such as alpha 3 beta 1 or alpha 6 beta 4. Several anti-CD151 mAbs (monoclonal antibodies) have been shown to display anti-metastatic activity in vivo. Inhibition of metastasis was not attributed to any effect of these mAbs on tumour cell growth, but was essentially attributed to inhibition of cell motility. We have generated anti-CD151 mAbs which can inhibit the tumoral growth in different xenograft cancer models. As expected, these mAbs were also able to inhibit metastasis in orthotopic cancer models. These data suggest that CD151 could function at multiple cancer stages, including not only metastasis cascade steps, but also earlier steps of primary tumour growth, thus reinforcing the interest of this innovative target in oncology. mAbs targeting CD151 may be of significant interest for cancer biotherapy.