期刊
FASEB JOURNAL
卷 16, 期 8, 页码 1266-+出版社
WILEY
DOI: 10.1096/fj.01-0911fje
关键词
metastasis; breast cancer; bone tropism; vitronectin receptor
The reasons why tumor cells metastasize to bone remain obscure. There is some evidence to support the theory that integrins (acting as cell surface adhesion receptors) play a role in mediating metastasis in certain organs. Here, we report that overexpression of a functionally active integrin alphavbeta3 in Chinese hamster ovary (CHO) tumor cells drastically increased the incidence, number, and area of bone metastases in nude mice compared with those observed in mock-transfected CHO cells (CHO dhfr(+)) or in CHO cells expressing a functionally inactive integrin alphavbeta3 (CHO 3 744). Moreover, a breast cancer cell line (B02) established from bone metastases caused by MDA-MB-231 cells constitutively overexpressed integrin alphavbeta3, whereas the cell surface expression level of other integrins remained unchanged. In vivo, the extent of bone metastases in B02-bearing mice was significantly increased compared with that of MDAMB-231-bearing mice. In vitro, B02 cells and CHO cells expressing a functionally active integrin alphavbeta3 exhibited substantially increased invasion of and adhesion to mineralized bone, bone sialoprotein, and collagen compared with those found with MDA-MB-231, CHO dhfr(+), and CHO 3 744 cells, respectively. Overall, our findings suggest that integrin alphavbeta3 expression in tumor cells accelerates the development of osteolytic lesions, presumably through increased invasion of and adhesion to bone.
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