A test of the role of alpha5 integrin/fibronectin interactions in tumorigenesis

Published data show that reduction or loss of fibronectin or its receptor, alpha5beta1 integrin, occurs frequently in tumors and transformed cells. Furthermore, restoration of these adhesion proteins has been reported to reduce tumorigenesis. These results suggest that fibronectin/alpha5beta1 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 genetically altered in the genes for fibronectin or alpha5 integrin. Our results show that heterozygosity for either does not lead to an increased incidence of tumors, alteration in tumor spectrum, or increased levels of metastasis, even when the fibronectin or alpha5 mutations are combined with mutations in the p53 tumor suppressor gene that lead to spontaneous tumor formation and could also cause loss of heterozygosity. Furthermore, loss of heterozygosity for alpha5 was not a common concomitant of tumorigenesis or metastasis. Finally, chimeric animals containing high proportions of alpha5-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 alpha5beta1 integrin does not contribute to tumorigenesis or metastasis.