Platelet-Derived Growth Factor-B Enhances Glioma Angiogenesis by Stimulating Vascular Endothelial Growth Factor Expression in Tumor Endothelia and by Promoting Pericyte Recruitment

Abstract

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.

Accelerated fracture healing in the geriatric, osteoporotic rat with recombinant human platelet‐derived growth factor‐bb and an injectable beta‐tricalcium phosphate/collagen matrix

“…Additionally, rhPDGF-BB will promote new blood vessel formation, a critical element in fracture repair through the upregulation of VEGF. 16 Moreover, PDGF will stabilize newly formed capillaries at the healing wound through its effect on pericytes. 30,31 Consequently, the osteogenic and angiogenic properties of rhPDGF-BB could significantly improve fracture healing in geriatric and osteoporotic patients.…”

“…12 PDGF-BB is chemotactic and mitogenic for osteoblast lineage cells and osteoblasts [13][14][15] and therefore may enhance fracture healing by attracting osteoprogenitor cells to the fracture by chemotaxis and amplifying their quantity by mitogenesis. Further, PDGF-BB upregulates the expression of angiogenic vascular endothelial growth factor (VEGF), 16 a key molecule for bone regeneration. 17 Consequently, the biological properties of PDGF underscore the logic for its use to enhance bone wound healing for patients who may be compromised wound healers.…”

Recombinant human platelet‐derived growth factor BB (rhPDGF‐BB) and beta‐tricalcium phosphate/collagen matrix enhance fracture healing in a diabetic rat model

“…19 Further, PDGF has chemotactic and proliferative properties while purportedly suppressing differentiation of osteoprogenitor cells. 35 An additional crucial wound healing property of rhPDGF-BB is the promotion of new blood vessel formation through up-regulation of VEGF 42 and stabilization of new capillaries by mural cells. 43 VEGF is expressed by proliferating osteoblasts and hypertrophic chondrocytes and is a key regulator of endochondral bone formation.…”

Pericytes and Endothelial Precursor Cells: Cellular Interactions and Contributions to Malignancy

“…In a fibrosarcoma model, PDGF-h was identified as an important factor in the recruitment of pericytes to tumor vessels (20). In human gliomas, PDGF-h and PDGF receptor h (PDGF-Rh) are overexpressed, and in mice, the overexpression of PDGF-h enhanced glioma formation by attracting pericytes (21).…”