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Review
. 2020 May;57(5):2461-2478.
doi: 10.1007/s12035-020-01892-8. Epub 2020 Mar 9.

Tumor Development and Angiogenesis in Adult Brain Tumor: Glioblastoma

Bhavesh K Ahir  1 , Herbert H Engelhard  2 , Sajani S Lakka  3
Affiliations
Review

Tumor Development and Angiogenesis in Adult Brain Tumor: Glioblastoma

Bhavesh K Ahir et al. Mol Neurobiol. 2020 May.

Abstract

Angiogenesis is the growth of new capillaries from the preexisting blood vessels. Glioblastoma (GBM) tumors are highly vascularized tumors, and glioma growth depends on the formation of new blood vessels. Angiogenesis is a complex process involving proliferation, migration, and differentiation of vascular endothelial cells (ECs) under the stimulation of specific signals. It is controlled by the balance between its promoting and inhibiting factors. Various angiogenic factors and genes have been identified that stimulate glioma angiogenesis. Therefore, attention has been directed to anti-angiogenesis therapy in which glioma proliferation is inhibited by inhibiting the formation of new tumor vessels using angiogenesis inhibitory factors and drugs. Here, in this review, we highlight and summarize the various molecular mediators that regulate GBM angiogenesis with focus on recent clinical research on the potential of exploiting angiogenic pathways as a strategy in the treatment of GBM patients.

Keywords: Angiogenesis; Anti-angiogenesis therapy; Clinical trials in glioblastoma (GBM); Glioblastoma (GBM); Tumor development.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Schematic representation of angiogenic events in GBM. (a) Angiogenesis processes are initiated by the angiogenic factors, which are being released from the GBM cells in the hypoxic tumor microenvironment. The major angiogenic factors are involved in GBM angiogenesis process which includes the VEGF, FGF, HIF1α, and Ang-1 and Ang-2. (b) These angiogenic factors bind to their receptors on endothelial cells and then start to initiate the endothelial cell proliferation and migration. During the endothelial cell proliferation and migration processes, the ECM start to degrade, and the endothelial cells are assembled into a tube/vessel-like structure. (c) The final step of GBM angiogenesis process is the maturation of the blood vessel wall, which is constructed by the recruitment of pericytes to cover the endothelial cells from its outside to form a new blood vessel formation
Fig. 2
Fig. 2
Angiogenic factors and receptors involved in GBM angiogenesis. VEGFR, PDGF, EGFR, and FGFR involved in the key molecular signaling events (RAS/RAF/MEK/MAPK signaling pathway and PI3K/AKT/mTOR signaling pathway) which plays an important role in glioma cells proliferation, migration, and survival
See this image and copyright information in PMC

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