Functional Significance of Vascular Endothelial Growth Factor Receptor Expression on Human Glioma Cells

Abstract

Vascular endothelial growth factor (VEGF) is one of the most important angiogenesis factors. In many tumors, VEGF plays a pivotal role for their vascularization and is necessary to supply the malignant tissue with oxygen and nutrients. However, VEGF receptors (VEGFR) have recently been detected also on some tumor cells, and autocrine mitogenic effects of VEGF have been suspected. Since glioma cells are known to produce large amounts of VEGF, we investigated VEGFR-expression and effects of VEGF on glioma cells. The three glioma cell lines and eight glioma cells cultivated from WHO grade IV gliomas investigated strongly expressed VEGF121 and VEGF165, but weakly either VEGFR-1 or -2, sometimes for both, as evidenced by reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry. Quantitative RT-PCR revealed a 1000- to 50-fold lower expression of VEGFR than in cultivated human umbilical vein endothelial cells. In two glioma cell lines analyzed, VEGF induced a weak tyrosine phosphorylation of the VEGFR, but downstream signal transduction effects on the mitogen-activated protein kinases p42/p44 or transcription factors like AP-1 or NFKB were within the background of the methods. In accordance, VEGF or the VEGFR agonists VEGF-D or placenta growth factor (P1GF) did not produce significant effects on glioma cell proliferation or VEGF production. We conclude that despite a low expression of VEGFR in some glioma cells functional effects are low and autocrine growth stimulatory effects within a glioma are minor.

Phosphorylated KDR expression in endometrial cancer cells relates to HIF1α/VEGF pathway and unfavourable prognosis

“…16 Cancer cell reactivity was thought to represent VEGF content, as KDR was thought to be confined to endothelial cells, despite reports suggesting the presence of KDR in a variety of human tumours, including breast, lung and endometrial carcinomas. [9][10][11][12][13] Constitutive expression of KDR, however, may not necessarily mean an active KDR pathway.…”

“…7,8 Cancer cells and intratumoral endothelium have also been reported to express VEGF receptors. [9][10][11][12][13] The expression of VEGFRs, however, does not necessarily mean active participation in cancer or endothelial cell biology as this can only be analysed by assessing the activated forms of these receptors. Brekken et al 14 produced monoclonal antibodies that preferentially recognize VEGF bound to its receptor KDR, which presumably reflects the activated KDR receptor.…”

Endoglin expression in metastatic breast cancer cells enhances their invasive phenotype

“…Immunocytochemistry and immunoelectron microscopy For light microscopy, cells grown on poly-D-lysine-coated coverslips for 2 days were fixed with À20 1C cold acetone, immunostained with anti-endoglin (1:250 in phosphate-buffered saline (PBS), rabbit polyclonal antibody; Santa Cruz Biotechnology, Santa Cruz, CA, USA, sc-20632) and nuclei counterstained with hemalaun (Mentlein et al, 2004 …”

Biological Markers of Recurrence and Survival of High-Grade Gliomas: The Role of Hepatocyte Growth Factor

“…Cancers that express VEGF grow and metastasize, VEGF belongs to platelet-derived growth factor family. They are involved in both, vasculogenesis, the novo, and angiogenesis (Mentlein et al, 2004;Reux et al, 2006). Within the major growth factors related to angiogenesis, VEGF is one of the most important.…”