Taverna D, Ullman-Culleré M, Rayburn H, Bronson R T, Hynes R O
Howard Hughes Medical Institute and Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Cancer Res. 1998 Feb 15;58(4):848-53.
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.
已发表的数据表明，纤连蛋白或其受体α5β1整合素的减少或缺失在肿瘤和转化细胞中频繁发生。此外，据报道，这些黏附蛋白的恢复可减少肿瘤发生。这些结果表明，纤连蛋白/α5β1相互作用可能起到抑制肿瘤发展或进展的作用。为了在自发肿瘤形成的背景下验证这一假设，我们分析了纤连蛋白或α5整合素基因发生遗传改变的小鼠的肿瘤发展情况。我们的结果表明，即使纤连蛋白或α5突变与p53肿瘤抑制基因的突变相结合，导致自发肿瘤形成并可能导致杂合性缺失，二者的杂合性缺失均不会导致肿瘤发生率增加、肿瘤谱改变或转移水平升高。此外，α5的杂合性缺失并非肿瘤发生或转移的常见伴随现象。最后，含有高比例α5缺失细胞的嵌合动物并未表现出肿瘤发生率增加或肿瘤进展改变。我们得出结论，在此处研究的遗传背景下，纤连蛋白或α5β1整合素的缺失不会促进肿瘤发生或转移。
