Integrin alpha 5 beta 1: a potent inhibitor of experimental lung metastasis

The integrin alpha 5 beta 1 seems to be the most relevant receptor of tumor cells for binding to fibronectin, Although numerous studies suggest a role of tumor cell fibronectin interaction in tumor metastasis, differential in tegrin expression on tumor cells has, however, not been correlated with met astatic capabilities, We addressed this question by transfection of the int egrin alpha 5 beta 1 cDNA into HT-29 human colon carcinoma cells which led to de novo expression of functional integrin alpha 5 beta 1. Similar to oth er reports, expression of the integrin alpha 5 beta 1 in HT-29 tumor cells exerted an inhibitory action on sell proliferation as indicated in our stud y by formation of fewer colonies in soft agar, The tumor growth inhibitory property of the integrin alpha 5 beta 1 was also shown by reduction of subc utaneous xenograft growth in nude mice to approximately 50% of that of cont rol transfectants, For the first time, we found that several clones of inte grin alpha 5 subunit transfectants displayed dramatically reduced formation of lung colonies and cutaneous metastasis after intravenous injection into nude mice, While most animals inoculated with control transfectant cells f ormed macroscopically visible lung colonies ranging from 12.6 +/- 2.6 to 22 .0 +/- 6.6 (mean colony number +/- SEM), mice inoculated with HT-29 cell cl ones expressing the integrin alpha 5 beta 1 were almost completely free of lung colonies (ranging from 0.0 +/- 0 to 0.2 +/- 0.1). Our results imply th at integrin alpha 5 beta 1 expression inhibits circulating tumor cells in p ursuing late steps of the metastatic process as represented by the artifici al metastasis (lung colonisation) model, (C) 1998 Kluwer Academic Publisher s.