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Abstract

Vascular endothelial growth factor (VEGF), a potent angiogenic and vascular permeability factor, is important in the angiogenesis of glioblastoma. A major difference between pilocytic astrocytoma, a grade I tumor, and the grade II fibrillary astrocytoma is the vascular proliferation, highly vascularized stroma, and great propensity for cyst formation in the former. In order to explore factors regulating such angiogenesis and cyst formation in pilocytic astrocytoma, we examined expression of VEGF and its receptors (KDR and Flt-1) using in situ hybridization. In all 14 cases a high level of VEGF transcripts could be demonstrated. These were found in specific regions, namely, in the tumor cyst wall, in areas of hyaline cystic degeneration, in stellate reticulated astrocytes around microcysts in the biphasic compact and loose areas, and in tumor cells with degenerative pleomorphic multicoated nuclei. KDR and Flt-1 were expressed in the tumor vasculature, with particularly high levels seen in coiled young proliferating vessels, especially those in the cyst wall. Given the known angiogenic and vascular permeability activities of VEGF, we propose that VEGF plays an important role in molding the characteristic morphologic features of this tumor, namely, the formation of cysts, microcystic pattern, hyaline cystic degeneration, hyaline vessels, and vascular proliferation. Mechanisms that block the VEGF pathway could constitute a potential therapeutic strategy for the treatment of this tumor.

Tumor angiogenesis and anti-angiogenic therapy in malignant gliomas revisited

“…However, this putative mechanism requires the co-expression of c-met together with VEGFR-2 on glioma cells in vivo. Whereas VEGFR-2 can be readily detected in glioma cell lines in vitro, most studies suggest that in both murine and human glioma specimens in vivo expression of VEGFR-2 is mainly confined to vascular endothelial cells [51, 52, 77, 87, 112–114, 136], and potentially to a subset of cancer stem-like cells [49]. As such, it remains currently unclear whether the mechanism of bevacizumab-induced migration of glioma cells as proposed by Lu et al is of relevance in human glioblastoma in vivo.…”

Expression of Chemokines and Chemokine Receptors in Brain Tumor Tissue Derived Cells

“…MCP-1 is reported to be upregulated in GBM and anaplastic astrocytoma and mediates the recruitment of macrophages with proangiogenic functions into tumor area in the gliomas (Leung et al, 1997;Lee et al, 2005). Dwyer et al demonstrated that IL-8 has the ability to function as an angiogenic factor in glioblastoma (Dwyer et al, 2012).…”

The ecology of brain tumors: lessons learned from neurofibromatosis-1

“…A dynamic relationship forms between the pre-neoplastic/ neoplastic and non-neoplastic stromal cell populations through stromagen and gliomagens release, which together facilitate tumorigenesis, tumor maintenance and glioma progression. endothelial growth factor (Forstreuter et al, 2002;Kerber et al, 2008), hepatocyte growth factor (Badie et al, 1999;Kunkel et al, 2001), monocyte chemoattractant protein-1 (Martinet et al, 1992;Leung et al, 1997) and the chemokine CX3CL1 (fractalkine) through activation of the CX3CR1 receptor (Held-Feindt et al, 2010). Monocyte chemoattractant protein-1 can also increase the surface expression of CX3CR1 on microglia (Green et al, 2006), thus providing amplification circuits for further microglia recruitment.…”