Dual pathways of tubular morphogenesis of vascular endothelial cells by human glioma cells: vascular endothelial growth factor/basic fibroblast growth factor and interleukin-8

Jpn J Cancer Res. 1995 Dec;86(12):1189-97. doi: 10.1111/j.1349-7006.1995.tb03314.x.


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 fibroblast 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-beta mRNA than IN157 cells, whereas the two had similar levels of transforming 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 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Astrocytoma / metabolism
  • Astrocytoma / pathology
  • Cells, Cultured
  • Coculture Techniques
  • Endothelial Growth Factors / pharmacology
  • Endothelial Growth Factors / physiology*
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / drug effects
  • Fibroblast Growth Factor 2 / pharmacology
  • Fibroblast Growth Factor 2 / physiology*
  • Glioma / metabolism
  • Glioma / pathology*
  • Humans
  • Interleukin-8 / pharmacology
  • Interleukin-8 / physiology*
  • Lymphokines / pharmacology
  • Lymphokines / physiology*
  • Morphogenesis / drug effects
  • Neoplasm Proteins / physiology
  • Neovascularization, Pathologic / physiopathology*
  • Omentum / blood supply
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Interleukin-8
  • Lymphokines
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Fibroblast Growth Factor 2