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

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Abstract
To investigate the role of β1 integrin during tumor metastasis, we established a ras-myc transformed fibroblastoid cell line with a disrupted β1 integrin gene on both alleles (GERM 11). Stable transfection of this cell line with an expression vector encoding β1A integrin resulted in β1A integrin-expressing sublines. Tumors were induced by subcutaneous injection of GERM 11 cells and 3 independent β1 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 β1 integrin expression. The metastasis potential of all three β1 integrin-expressing GERM 11 sublines tested was significantly higher than that of the β1-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. β1 integrin, therefore, increases but is not essential for metastasis of ras-myc transformed fibroblasts.