Dual Pathways to Tubular Morphogenesis of Vascular Endothelial Cells by Human Glioma Cells: Vascular Endothelial Growth Factor/Basic Fibroblast Growth Factor and Interleukin‐8

Abstract

In this study, we examined whether human glioma cells are angiogenic in a model using human microvascular endothelial cells, and also which factor is responsible for the glioma‐dependent angiogenesis. Tubular morphogenesis 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 fihroblast growth factor (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 cells had much higher levels of VEGF, bFGF and transforming growth factor‐(mRNA than IN157 cells, whereas the two had similar levels of transforming growth factor‐Alfa 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 the inhibition was almost complete when anti‐VEGF and anti‐bFGF antibodies were present. On the other hand, IN157‐dependent tubular morphogenesis was inhibited by anti‐IL‐8 antibody, but not by anti‐VEGF or anti‐bFGF antibodies. These findings demonstrated dual paracrine controls of tumor angiogenesis by human glioma cells. One is mediated through VEGF and/or bFGF, and the other, through IL‐8.