Mechanisms of angiogenesis in gliomas

Abstract

Gliomas are the most frequent primary tumors of the central nervous system in adults. Glioblastoma multiforme, the most aggressive form of astrocytic tumors, displays a rapid progression that is accompanied by particular poor prognosis of patients. Intense angiogenesis is a distinguishing pathologic characteristic of these tumors and in fact, glioblastomas are of the most highly vascularized malignant tumors. For this reason, research and therapy strategies have focused on understanding the mechanisms leading to the origin of tumor angiogenic blood vessels in order to develop new approaches that effectively block angiogenesis and cause tumor regression. We discuss here some important features of glioma angiogenesis and we present molecules and factors and their possible functions and interactions that play a role in neovascularization. In spite of the great progress that molecular biology has achieved on investigating tumor angiogenesis, many aspects remain obscure and the complexity of the angiogenic process stands for an obstacle in identifying the exact and complete molecular pathways orchestrating new blood vessels formation, which are necessary for the survival and expansion of these tumors.

Inhibitor of DNA binding-4 promotes angiogenesis and growth of glioblastoma multiforme by elevating matrix GLA levels

“…Destroying or inhibiting tumor vasculature has a far-reaching effect in that the disruption of a single blood vessel can compromise the viability of tumor cells well beyond those cells that are immediately proximal to the vessel (Folkman, 1971). In this regard, identifying targets for anti-angiogenesis therapy may be of particular importance for improving the treatment of GBM, a highly vascularized, lethal, solid tumor (Folkman, 1971;Holland, 2000;Kargiotis et al, 2006). ID family members including ID1, ID2, and ID3 have identified functions in tumor progression, including angiogenesis, invasion, and metastasis (Lyden et al, 1999;Benezra, 2001;Benezra et al, 2001;Folkman, 2002;Ruzinova and Benezra, 2003;, and in other circumstances ID1 and ID2 may function as tumor suppressors in rodents (Itahana et al, 2003;Sikder et al, 2003;Russell et al, 2004).…”

Endosialin (CD248) is a marker of tumor-associated pericytes in high-grade glioma

“…19 Next, we combined immunofluorescent double labeling of formalin-fixed paraffin-embedded sections with high resolution confocal imaging of thin (B0.5 mm) optical sections. Costaining of these sections with the anti-endosialin monoclonal antibody B1/35 and with an antibody against the endothelium-specific marker CD34 revealed a clear separation of the two antibodies, with the endosialin-positive cells lying adjacent to the endothelial cells.…”

TNF-α and the IFN-γ-inducible protein 10 (IP-10/CXCL-10) delivered by parvoviral vectors act in synergy to induce antitumor effects in mouse glioblastoma

“…7 A hallmark of glioblastoma is the high degree of neovascularization observed within the tumor. [8][9][10] Inhibition of angiogenesis might be a powerful strategy for impeding the growth of vascularized tumors. The therapeutic effectiveness of targeting glioma-induced angiogenesis has indeed been demonstrated in various experimental systems.…”