Travers H, French N S, Norton J D
Cancer Research Campaign, Department of Gene Regulation, Paterson Institute for Cancer Research, Christie Hospital National Health Service Trust, Manchester, United Kingdom.
Cell Growth Differ. 1996 Oct;7(10):1353-60.
Transformed fibroblasts exhibit reduced adhesion to substrata, a characteristic attributable in part to reduced expression/increased degradation of extracellular matrix (EM) proteins such as type I collagen. To directly assess the role of EM proteins in cellular transformation, a vKRas-transformed mouse fibroblast cell line was transfected with an alpha 2(I) collagen expression construct. Stable transfectants displaying a partial restoration of type I collagen expression showed a flatter morphology with increased adherence to the substratum. These clones also exhibited a reduced ability to clone in soft agar, slower growth kinetics, and suppression of tumorigenicity in nude mice. Restoration of type I collagen is correlated with down-regulation of ras oncogene-responsive NVL3 VL30 gene expression. These results suggest that in addition to suppressing tumorigenicity by promoting cellular adhesion and cytoskeletal organization, EM proteins such as type I collagen may also act to subvert oncoprotein signaling pathways associated with the malignant phenotype.
转化的成纤维细胞对基质的黏附性降低，这一特性部分归因于细胞外基质（EM）蛋白（如I型胶原）的表达减少/降解增加。为了直接评估EM蛋白在细胞转化中的作用，用α2（I）胶原表达构建体转染vKRas转化的小鼠成纤维细胞系。显示I型胶原表达部分恢复的稳定转染子呈现更扁平的形态，对基质的黏附性增加。这些克隆在软琼脂中的克隆能力也降低，生长动力学较慢，并且在裸鼠中致瘤性受到抑制。I型胶原的恢复与ras癌基因反应性NVL3 VL30基因表达的下调相关。这些结果表明，除了通过促进细胞黏附和细胞骨架组织来抑制致瘤性外，I型胶原等EM蛋白还可能作用于颠覆与恶性表型相关的癌蛋白信号通路。
