Vascular endothelial growth factor in human glioma cell lines: induced secretion by EGF, PDGF-BB, and bFGF

Abstract

Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) is an endothelial cell-specific mitogen that is structurally related to platelet-derived growth factor (PDGF). Vascular endothelial growth factor/vascular permeability factor induces angiogenesis in vivo and may play a critical role in tumor angiogenesis. Using immunohistochemical analysis, the authors demonstrated the presence of VEGF/VPF protein in surgical specimens of glioblastoma multiforme and cultured glioma cells. By means of an enzyme-linked immunosorbent assay (ELISA) of cell supernatants, the authors showed that VEGF/VPF is variably secreted by all nine cultured human malignant glioma cell lines (CH-235MG, D-37MG, D-54MG, D-65MG, U-87MG, U-105MG, U-138MG, U-251MG, U-373MG) and by a single meningioma cell line (CH-157MN). An immunocytochemical survey of these cell lines revealed a cytoplasmic and cell-surface distribution of VEGF/VPF. In the U-105MG glioma cell line, VEGF/VPF secretion was induced with physiological concentrations of epidermal growth factor, PDGF-BB, or basic fibroblast growth factor, but not with PDGF-AA. Moreover, it was observed that activation of convergent growth factor signaling pathways led to increased glioma VEGF secretion. Similar results were obtained using these growth factor combinations in the D-54MG glioma cell line. The data obtained suggest a potential role for VEGF/VPF in tumor hypervascularity and peritumoral edema. These observations may lead to development of new therapeutic strategies.

FGF-2 and FGF-1 expressed in rat bladder carcinoma cells have similar angiogenic potential but different tumorigenic properties in vivo

“…VEGF has been reported to act in synergy with FGF-2 in the induction of angiogenesis in vitro (Pepper et al, 1992). Although exogeneously added FGF-2 might upregulate VEGF expression (Tsai et al, 1995), our results indicate that constitutive expression of FGF-1 or FGF-2 regulates VEGF expression leading to a reduced concentration. However VEGF content of cell cultured in vitro does not necessarily re¯ect their angiogenic and tumorigenic potential since hypoxia might modulate in vivo VEGF expression dierently from one cell line to the other.…”

Inhibitory effect on expression of angiogenic factors by antiangiogenic agents in renal cell carcinoma

“…Several experiments have demonstrated that expression of VEGF and bFGF is upregulated by various factors, including cytokines and hypoxia (Tsai et al, 1995;White et al, 1995;Claffey and Robinson, 1996). Therefore, we investigated whether EGF and hypoxia could induce VEGF and bFGF expression in human RCC cell lines and whether genistein could regulate the expression of these angiogenic factors under stimulation of EGF and hypoxia.…”

Regulation of vascular endothelial growth factor expression in human colon cancer by interleukin-1β

“…Several cytokines and growth factors are known to affect VEGF expression as well. Factors shown to increase VEGF expression in tumour cells include tumour necrosis factor, transforming growth factor-α, epidermal growth factor, IGF-I and PDGF-BB (Akagi et al, 1998;Tsai et al, 1995;Ryuto et al, 1996). However, not all of these factors increase VEGF expression in all tumour systems, i.e.…”