Angiogenesis and expression of PDGF‐C, VEGF, CD105 and HIF‐1α in human glioblastoma

Abstract

Glioblastoma (GBM), the most frequent and aggressive brain tumor, is characterized by marked angiogenesis directly related to invasiveness and poor prognosis. Hypoxia is considered to be an important stimulus for angiogenesis by inducing hypoxia-inducible factor 1-alpha (HIF-1α) overexpression that activates platelet-derived growth factor (PDGF) and VEGF. The aim of this study is to analyze the expression of PDGF-C, VEGF in endothelial and tumor cells of GBM and their relation to HIF-1α expression. Two hundred and eight GBM cases were studied by tissue microarray immunohistochemical preparation. Expression of HIF-1α, VEGF and PDGF-C was observed in 184 (88.5%), 131 (63%) and 160 (76.9%) tumor cases, respectively. The numbers of vessels were quantified by CD34, PDGF-C, VEGF and CD105 staining, and were in median 20, 16, 5 and 6, respectively. The GBMs that showed positive or negative expression for HIF-1α showed a median vascular density of 30 and 14, respectively, for CD34 (P < 0.015). Positive expression for HIF-1α was correlated with VEGF and PDGF-C expression in tumors (P < 0.001). There was a significant correlation between VEGF and PDGF-C expression in the cytoplasm of GBM tumor cells (P < 0.0001). We showed that VEGF expression in tumor cells was correlated with its expression in blood vessels (P < 0.0001). Endothelial cells with PDGF-C and VEGF positive expression were also positive for CD105 and their nuclei for Ki-67, confirming the neoangiogenic and proliferative influence of VEGF and PDGF-C. VEGF nuclear staining in tumor cells (P = 0.002) as well as nuclear staining for HIF-1α and VEGF (P = 0.005) correlated with survival. In summary, our present findings of the concomitant upregulation of PDGF-C with VEGF in GBM tumor cells and vessels further reinforce the benefit of using combined anti-angiogenic approaches to potentially improve the therapeutic response for GBM.

PDGF-CC underlies resistance to VEGF-A inhibition and combinatorial targeting of both suppresses pathological angiogenesis more efficiently

“…It was identified almost twenty years after the discovery of PDGF-A and PDGF-B [7, 8]. PDGF-CC is abundantly expressed by different types of cells, such as tumor cells [9, 10], endothelial cells (ECs) [11, 12], vascular smooth muscle cells (VSMCs) [12, 13], pericytes, fibroblasts [12, 14], and macrophages [15]. PDGF-CC binds to PDGFR-α and PDGFR-β [12], which are also expressed by many different cell types, including tumor cells [16, 17], VSMCs, pericytes, and fibroblasts [18], all of which play important roles in angiogenesis.…”

Correlation between chromosome 1p/19q status and VEGF mRNA expression in gliomas

“…Additionally, VEGF is an independent prognostic factor for astrocytoma. VEGF overexpression has been frequently overexpressed in glioblastoma and tumor cells, suggesting that VEGF might promote the growth of gliomas through angiogenesis (Clara et al, 2014). Moreover, the currently employed anti-angiogenic approaches that focus on the downregulation of VEGF are also believed to be effective against gliomas.…”

Role of traditional chinese medicine and its chemical components in anti-tumor metastasis

“…[30] Nowadays, compounds screened to inhibit tumor angiogenesis are provided with antitumor metastasis effects. Some models not only can be observed from histomorphology, [42] but also there are some neovascularization-related epithelial cell promoting factors, such as EGF, [43] VEGF, [44] FGF-2, [45] platelet-derived growth factor (PDGF), [46] platelet derived-endothelial cell growth factor-thymidine phosphorylase (PD-ECGF/TP) [47] and endothelin, [48] among which VEGF presents the most significant promoting effects on new vessels epithelial cells. [49] Normal epithelial cells can secrete these cell factors and so do some tumor cells.…”