Ruoslahti E
Cancer Research Center, La Jolla Cancer Research Foundation, Calif 92037, USA.
Invasion Metastasis. 1994;14(1-6):87-97.
Fibronectin and the alpha 5 beta 1 integrin play complex roles in malignancy. While normal cells usually deposit a fibronectin matrix around themselves, malignant cell lines often fail to do so. Decreased expression of the alpha 5 beta 1 integrin, which directs fibronectin matrix deposition, is one of the reasons for deficient matrix deposition. The defect can be corrected by expression of additional alpha 5 beta 1 from transfected cDNAs and exacerbated by selecting cells for loss of all alpha 5 beta 1. Tumorigenicity is suppressed in the alpha 5 beta 1 overexpressors and enhanced in the alpha 5 beta 1-negative cells. Synthetic peptides that bind to the alpha 5 beta 1 and other integrins can modulate their functions and suppress malignancy and metastasis in vivo. The signaling mechanisms that underlie these tumor-suppressive effects of the fibronectin matrix and the integrins are an important target for ongoing study.
纤连蛋白和α5β1整合素在恶性肿瘤中发挥着复杂的作用。正常细胞通常会在自身周围沉积纤连蛋白基质，而恶性细胞系往往无法做到这一点。指导纤连蛋白基质沉积的α5β1整合素表达降低是基质沉积不足的原因之一。通过转染的cDNA表达额外的α5β1可以纠正这种缺陷，而选择所有α5β1缺失的细胞则会使其加剧。α5β1过表达细胞的致瘤性受到抑制，而α5β1阴性细胞的致瘤性增强。与α5β1和其他整合素结合的合成肽可以调节它们的功能，并在体内抑制恶性肿瘤和转移。纤连蛋白基质和整合素这些肿瘤抑制作用背后的信号传导机制是正在进行研究的一个重要靶点。
