DUAL PATHWAYS TO TUBULAR MORPHOGENESIS OF VASCULAR ENDOTHELIAL-CELLS BY HUMAN GLIOMA-CELLS - VASCULAR ENDOTHELIAL GROWTH-FACTOR BASIC FIBROBLAST GROWTH-FACTOR AND INTERLEUKIN-8

In this study, we examined whether human glioma cells are angiogenic i n a model using human microvascular endothelial cells, and also which factor is responsible for the glioma-dependent angiogenesis. Tubular m orphogenesis in type I collagen gel by human microvascular endothelial cells was stimulated in the presence of 10 and 100 ng/ml of vascular endothelial growth factor (VEGF), 10 ng/ml basic fibroblast growth fac tor (bFGF) and 10 ng/ml of interleukin-8 (IL-8), Tube formation of the microvascular endothelial cells was assayed in the glioma cell lines IN157 and IN301, co-cultured using the double chamber method, IN301 ce lls had much higher levels of VEGF, bFGF and transforming growth facto r-beta mRNA than IN157 cells, whereas the two had similar levels of tr ansforming growth factor-alpha mRNA, By contrast, IN157 cells had much higher levels of IL-8 mRNA than IN301 cells. IN301-dependent tubular morphogenesis was inhibited by anti-VEGF or anti-bFGF antibody, and th e inhibition was almost complete when anti-VEGF and anti-bFGF antibodi es were present. On the other hand, IN157-dependent tubular morphogene sis was inhibited by anti-IL-8 antibody, but not by anti-VEGF or anti- bFGF antibodies. These findings demonstrated dual paracrine controls o f tumor angiogenesis by human glioma cells, One is mediated through VE GF and/or bFGF, and the other, through IL-8.