关键词: 乳腺癌, actin, CD44, MMP-2

Abstract: Objective To study the roles of actin and associated molecules in the control of human breast cancer cells malignant behaviors in vitro and in vivo. Methods A highly metastatic human breast cancer cell line BICR-H1 was compared with another breast cancer cell line MCF-7, which was well differentiated and non-metastatic. Western blot, immunofluorescence, gelatin zymography analysis and a chick embryonic chorioallantoic membrane (CAM) assay were used in this research. 5~30μg cisplatin or MMP-2 C terminal PEX domain were injected i.v. in CAM. Results BICR-H1 expressed high level of CD44, which was closely associated with actin aggregates at the bottom side of attached cells. It was also shown with MMP-2 activity. On the contrary, MCF-7 cells showed weak disruption of actin cytoskeleton structures and few actin aggregates. It expressed low or minimal level of CD44 and MMP-2. The expression of CD44 was down-regulated in cisplatin-treated BICR-H1 cells, and the activity of MMP-2 was also decreased upon PEX treatment. Both cell lines could form tumors in CAM, but only BICR-H1 cells could metastasize to distant tissues. Cisplatin inhibited the growth of BICR-H1 and MCF-7 cells in a time and dose dependent manner in CAM. The lung metastatic foci of BICR-H1 cells treated with 30μg cisplatin reduces from 30±15/embryo (PBS group) to 8±6/embryo, and the same dose of PEX can completely inhibits BICR-H1 metastasis. Conclusions It is concluded that actin cytoskeleton，CD44 and MMP-2 (ACM）molecular linkage is associated with breast cancer metastatic phenotypes, and that both cisplatin and PEX can interfere with the ACM molecular linkage, resulting in the suppression of both tumor growth and metastasis.

Key words: human breast cancer, actin cytoskeleton, CD44, matrix metalloproteinase-2