Reduced Blood Vessel Formation and Tumor Growth in α5-Integrin-negative Teratocarcinomas and Embryoid Bodies

摘要: Embryonic stem (ES) cells—wild-type, heterozygous, or null for α5-integrin—were injected ectopically into syngeneic mice to develop teratocarcinomas. α5-null-derived teratocarcinomas were significantly smaller than the wild-type α5 heterozygous tumors. Histological analysis revealed presence of tissues derived from all three germ layers, in However, α5-null displayed less undifferentiated tissue did controls. Decreased proliferation and increased apoptosis observed areas The expression extracellular matrix proteins, fibronectin tenascin-C, basement membrane components, laminin, entactin/nidogen, collagen IV, was similar different tumors, although deposition these molecules more disorganized absence α5-integrin various tumors confirmed by immunohistochemistry. Many vessels, but not all, stained positively α5-integrin, showing that they host derived. Analysis area occupied vessels revealed, on average, an 8-fold decrease compared with control Staining smooth muscle α-actin showed pericytes cells recruited around suggesting vessel differentiation. Deposition EIIIA EIIIB fact some, few, α5-integrin-negative existed indicated α5−/− ES could differentiate endothelial cells. Endothelial cell differentiation formation analyzed also vitro. differentiated embryoid bodies, delayed growth attachment. Differentiation achieved, organization a complex vasculature We conclude α5β1-integrin plays significant role both cultures Reduced vascularization likely contributed reduced