Narita T, Kimura N, Sato M, Matsuura N, Kannagi R
Laboratory of Experimental Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Anticancer Res. 1998 Jan-Feb;18(1A):257-62.
We investigated alterations in the expression of integrin on adriamycin-resistant MCF-7 (MCF-7/ADR) cells, which had been selected from MCF-7 human breast cancer cells, in order to examine the mechanisms behind the acquisition of malignancy in breast cancer progression. Expression of the alpha 6 integrin subunit of MCF-7/ADR cells was stronger than that of MCF-7 cells, whereas expression of alpha 2 integrin subunit of MCF-7/ADR cells was weaker than that of MCF-7 cells. MCF-7/ADR showed increased binding activity to laminin, but not to collagen or fibronectin, compared to those of parental MCF-7 cells. Adhesion of MCF-7 cells to collagen and laminin was inhibited by the addition of antibody to alpha 2 and alpha 6 integrin subunit, respectively. On the other hand, adhesion of MCF-7/ADR cells to collagen was not inhibited by the addition of antibody to alpha 2, alpha 3 or alpha 6 integrin subunit. Adhesion of MCF-7/ADR cells to laminin was inhibited by not only the antibody to alpha 6 subunit but also the antibody to the alpha 3 subunit. The transmigratory activity of MCF-7/ADR cells was higher than that of MCF-7 cells. A significant inhibitory effect on the transmigration of MCF-7/ADR cells was observed by the addition of antibody to alpha 6 and beta 1 integrin subunit. MCF-7/ADR cells appeared smaller and flatter than MCF-7 cells, and spread to a greater extent on the culture dish. MCF-7 cells cultured on Matrigel for 24 hours formed clusters. In contrast to this, MCF-7/ADR cells expanded with a tubular-like pattern on Matrigel. The spread of MCF-7/ADR cells was incompletely inhibited by addition of the antibody to alpha 3 integrin subunit, and completely inhibited by addition of the antibody to alpha 6 and beta 1 integrin subunit. These findings suggest that integrins on MCF-7/ADR cells are altered from those on parental MCF-7 cells in not only expression but also function, and that interaction between cancer cells and extracellular matrix protein is involved in augmentation of the invasiveness of MCF-7/ADR cells.
我们研究了从MCF-7人乳腺癌细胞中筛选出的阿霉素耐药MCF-7（MCF-7/ADR）细胞中整合素表达的变化，以探究乳腺癌进展过程中恶性程度增加背后的机制。MCF-7/ADR细胞的α6整合素亚基表达强于MCF-7细胞，而MCF-7/ADR细胞的α2整合素亚基表达弱于MCF-7细胞。与亲代MCF-7细胞相比，MCF-7/ADR对层粘连蛋白的结合活性增加，但对胶原蛋白或纤连蛋白的结合活性未增加。分别添加针对α2和α6整合素亚基的抗体可抑制MCF-7细胞与胶原蛋白和层粘连蛋白的黏附。另一方面，添加针对α2、α3或α6整合素亚基的抗体并不能抑制MCF-7/ADR细胞与胶原蛋白的黏附。MCF-7/ADR细胞与层粘连蛋白的黏附不仅受到针对α6亚基抗体的抑制，还受到针对α3亚基抗体的抑制。MCF-7/ADR细胞的迁移活性高于MCF-7细胞。添加针对α6和β1整合素亚基的抗体可观察到对MCF-7/ADR细胞迁移有显著抑制作用。MCF-7/ADR细胞比MCF-7细胞显得更小、更扁平，并且在培养皿上的铺展程度更大。在基质胶上培养24小时的MCF-7细胞形成细胞簇。与此相反，MCF-7/ADR细胞在基质胶上呈管状样扩展。添加针对α3整合素亚基的抗体可不完全抑制MCF-7/ADR细胞的铺展，而添加针对α6和β1整合素亚基的抗体可完全抑制其铺展。这些发现表明，MCF-7/ADR细胞上的整合素不仅在表达上而且在功能上都与亲代MCF-7细胞上的整合素不同，并且癌细胞与细胞外基质蛋白之间的相互作用参与了MCF-7/ADR细胞侵袭性的增强。
