Dual pathways of 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 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.
Wakabayashi
Y
Y
Department of Neurosurgery, Oita Medical University.
Shono
T
T
Isono
M
M
Hori
S
S
Matsushima
K
K
Ono
M
M
Kuwano
M
M
D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016228:Endothelial Growth Factors / Q000494:pharmacology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000502:physiology*; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology / Q000502:physiology*; D008222:Lymphokines / Q000494:pharmacology / Q000502:physiology*; D009024:Morphogenesis / Q000187:drug effects; D009363:Neoplasm Proteins / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D009852:Omentum / Q000098:blood supply; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D016209:Interleukin-8; D008222:Lymphokines; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2