Integrin αvβ3 expression confers on tumor cells a greater propensity to metastasize to bone

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.