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[整合素及整合素相关分子:抗转移疗法的开发靶点]

[Integrins and integrin-associated molecules: targets for the development of antimetastatic therapies].

作者信息

Velasco-Velázquez M A, Molina-Guarneros J A, Mendoza-Patiño N, Sullivan López J, Mandoki J J

机构信息

Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), México, D.F.

出版信息

Rev Invest Clin. 1999 May-Jun;51(3):183-93.

Abstract

Integrins are receptors that mediate cell adhesion and the formation of signaling complex. Changes in the expression of integrins are required during the following steps in the generation of metastases: a) angiogenesis; b) detachment from the primary tumor; c) tumor cell-platelet interaction; d) adhesion to vascular endothelium and e) proliferation. There is a correlation between invasive capability and changes in the expression of some proteins that are clustered in focal adhesion sites, as FAK, CD82, CD9 or CD63. Both, integrin blocking (using antibodies or RGD containing peptides), as well as induced changes in the expression of integrin-associated molecules, are able to inhibit formation of metastases. Discovery and characterization of molecules that regulate the adhesive capability of tumor cells, will lead to development of antimetastasic therapies. In the search of tumor dissemination inhibitors, integrins and some integrin-associated molecules are important pharmacological targets.

摘要

整合素是介导细胞黏附及信号复合物形成的受体。在转移发生的以下步骤中,整合素表达会发生变化:a) 血管生成;b) 从原发肿瘤脱离;c) 肿瘤细胞与血小板相互作用;d) 黏附于血管内皮;e) 增殖。侵袭能力与一些聚集在黏着斑部位的蛋白质(如黏着斑激酶、CD82、CD9或CD63)表达的变化之间存在关联。整合素阻断(使用抗体或含RGD的肽)以及整合素相关分子表达的诱导变化,均能够抑制转移的形成。对调节肿瘤细胞黏附能力的分子进行发现和表征,将引领抗转移疗法的发展。在寻找肿瘤扩散抑制剂的过程中,整合素及一些整合素相关分子是重要的药理学靶点。

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