A TEST OF THE ROLE OF ALPHA-5 INTEGRIN FIBRONECTIN INTERACTIONS IN TUMORIGENESIS/

Published data show that reduction or loss of fibronectin or its recep tor, alpha 5 beta 1 integrin, occurs frequently in tumors and transfor med cells, Furthermore, restoration of these adhesion proteins has bee n reported to reduce tumorigenesis. These results suggest that fibrone ctin/alpha 5 beta 1 interactions may act to suppress tumor development or progression. To test this hypothesis in the context of spontaneous tumor formation, we have analyzed tumor development in mice genetical ly altered in the genes for fibronectin or alpha 5 integrin. Our resul ts show that heterozygosity for either does not lead to an increased i ncidence of tumors, alteration in tumor spectrum, or increased levels of metastasis, even when the fibronectin or alpha 5 mutations are comb ined with mutations in the p53 tumor suppressor gene that lead to spon taneous tumor formation and could also cause loss of heterozygosity. F urthermore, loss of heterozygosity for alpha 5 was not a common concom itant of tumorigenesis or metastasis. Finally, chimeric animals contai ning high proportions of alpha 5-null cells did not show an increased incidence of tumors or a change in tumor progression. We conclude that , in the genetic backgrounds studied here, loss of fibronectin or alph a 5 beta 1 integrin does not contribute to tumorigenesis or metastasis .