Ruoslahti E
Cancer Research Center, La Jolla Cancer Research Foundation, CA 92037, USA.
Tumour Biol. 1996;17(2):117-24. doi: 10.1159/000217975.
Cell adhesion and migration are controlled by the level of alpha 5 beta 1 integrin (fibronectin receptor) and by the amount of fibronectin matrix around the cell; adhesion is promoted at all levels of integrin expression and matrix assembly, whereas high levels of either or both curb cell migration. The alpha 5 beta 1 integrin appears to be a growth-suppressing integrin, and it protects cells from apoptosis when growth factors are absent. In contrast, the alpha v beta 3 integrin (vitronectin receptor) cooperates with certain growth factors, potentiating their effect on cells. These effects of alpha 5 beta 1 and alpha v beta 3 depend on signaling pathways specific for these integrins; integrins have both common and specific pathways for signaling into the cell. Moreover, integrins require activation from the inside of the cell to be able to bind their ligand outside the cell. High alpha 5 beta 1 expression and abundant matrix formation also suppress tumorigenicity in vivo, whereas perturbing the function of alpha 5 beta 1 with peptides that block its ligand binding suppresses experimental metastasis. Effecting these changes in tumor cells by gene therapy or pharmacological approaches may provide useful new cancer therapies.
细胞黏附和迁移受α5β1整合素（纤连蛋白受体）水平以及细胞周围纤连蛋白基质数量的控制；在整合素表达和基质组装的各个水平上黏附均会增强，而其中任何一种或两者水平较高时都会抑制细胞迁移。α5β1整合素似乎是一种抑制生长的整合素，在缺乏生长因子时可保护细胞免于凋亡。相比之下，αvβ3整合素（玻连蛋白受体）与某些生长因子协同作用，增强它们对细胞的影响。α5β1和αvβ3的这些作用取决于这些整合素特有的信号通路；整合素具有传入细胞的共同和特定信号通路。此外，整合素需要从细胞内部激活才能结合细胞外的配体。高α5β1表达和丰富的基质形成也会在体内抑制肿瘤发生，而用阻断其配体结合的肽干扰α5β1的功能则会抑制实验性转移。通过基因治疗或药理学方法在肿瘤细胞中实现这些变化可能会提供有用的新型癌症治疗方法。
