beta 1 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 esta blished a ras-myc transformed fibroblastoid cell line with a disrupted beta 1 integrin gene on both alleles (GERM 11), Stable transfection of this cel l line with an expression vector encoding beta 1A integrin resulted in beta 1A integrin-expressing sublines. Tumors were induced by subcutaneous injec tion of GERM 11 cells and 3 independent beta 1 integrin expressing sublines (GERM 116, 1A10, 2F2) into syngeneic mice. After 10 days tumors were surgi cally removed. While average weights of GERM 11 and GERM 116 tumors were si milar, tumors induced by the high expressing clones 1A10 and 2F2 were marke dly smaller, suggesting an inverse correlation of tumor growth and beta 1 i ntegrin expression. The metastasis potential of all three beta 1 integrin-e xpressing 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 seve re metastasis in lung and liver, while GERM 11 tumors induced only a few me tastatic 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, lami nin-1, and collagen type I. beta 1 integrin, therefore, increases but is no t essential for metastasis of ras-myc transformed fibroblasts.