Platelet-derived growth factor-B enhances glioma angiogenesis by stimulating vascular endothelial growth factor expression in tumor endothelia and by promoting pericyte recruitment.
Platelet-derived growth factor (PDGF)-B and its receptor (PDGF-R) beta are overexpressed in human gliomas and responsible for recruiting peri-endothelial cells to vessels. To establish the role of PDGF-B in glioma angiogenesis, we overexpressed PDGF-B in U87MG glioma cells. Although PDGF-B stimulated tyrosine phosphorylation of PDGF-Rbeta in U87MG cells, treatment with recombinant PDGF-B or overexpression of PDGF-B in U87MG cells had no effect on their proliferation. However, an increase of secreted PDGF-B in conditioned media of U87MG/PDGF-B cells promoted migration of endothelial cells expressing PDGF-R beta, whereas conditioned media from U87MG cells did not increase the cell migration. In mice, overexpression of PDGF-B in U87MG cells enhanced intracranial glioma formation by stimulating vascular endothelial growth factor (VEGF) expression in neovessels and by attracting vessel-associated pericytes. When PDGF-B and VEGF were overexpressed simultaneously by U87MG tumors, there was a marked increase of capillary-associated pericytes as seen in U87MG/VEGF(165)/PDGF-B gliomas. As a result of pericyte recruitment, vessels induced by VEGF in tumor vicinity migrated into the central regions of these tumors. These data suggest that PDGF-B is a paracrine factor in U87MG gliomas, and that PDGF-B enhances glioma angiogenesis, at least in part, by stimulating VEGF expression in tumor endothelia and by recruiting pericytes to neovessels.
Guo
Ping
P
Department of Pathology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA.
Hu
Bo
B
Gu
Weisong
W
Xu
Li
L
Wang
Degui
D
Huang
Hui-Jen Su
HJ
Cavenee
Webster K
WK
Cheng
Shi-Yuan
SY
D000818:Animals; D000077214:Becaplermin; D002460:Cell Line; D016228:Endothelial Growth Factors / Q000235:genetics*; D004730:Endothelium, Vascular / Q000473:pathology*; D005910:Glioma / Q000098:blood supply*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008222:Lymphokines / Q000235:genetics*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D020286:Pericytes / Q000473:pathology / Q000502:physiology*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins / Q000494:pharmacology; D013552:Swine; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000077214:Becaplermin