β1 integrin promotes but is not essential for metastasis of ras-myc transformed fibroblasts

To investigate the role of beta 1 integrin during tumor metastasis, we established a ras-myc transformed fibroblastoid cell line with a disrupted beta 1 integrin gene on both alleles (GERM 11), Stable transfection of this cell line with an expression vector encoding beta 1A integrin resulted in beta 1A integrin-expressing sublines. Tumors were induced by subcutaneous injection of GERM 11 cells and 3 independent beta 1 integrin expressing sublines (GERM 116, 1A10, 2F2) into syngeneic mice. After 10 days tumors were surgically removed. While average weights of GERM 11 and GERM 116 tumors were similar, tumors induced by the high expressing clones 1A10 and 2F2 were markedly smaller, suggesting an inverse correlation of tumor growth and beta 1 integrin expression. The metastasis potential of all three beta 1 integrin-expressing GERM 11 sublines tested was significantly higher than that of the beta 1-deficient GERM 11 cells. GERM 116 tumors led in all animals to severe metastasis in lung and liver, while GERM 11 tumors induced only a few metastatic foci in the lung. Stroma of both tumors contained nidogen and high amounts of tenascin C, but only a few very low levels of fibronectin, laminin-1, and collagen type I. beta 1 integrin, therefore, increases but is not essential for metastasis of ras-myc transformed fibroblasts.