A Test of the Role of α5 Integrin/Fibronectin Interactions in Tumorigenesis¹

Published data show that reduction or loss of fibronectin or its receptor, α5β1 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/α5β1 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 α5 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 α5 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 α5 was not a common concomitant of tumorigenesis or metastasis. Finally, chimeric animals containing high proportions of α5-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 α5β1 integrin does not contribute to tumorigenesis or metastasis.