Tumor Vessels Fuel the Fire in Glioblastoma

Abstract

Glioblastoma, a subset of aggressive brain tumors, deploy several means to increase blood vessel supply dedicated to the tumor mass. This includes typical program borrowed from embryonic development, such as vasculogenesis and sprouting angiogenesis, as well as unconventional processes, including co-option, vascular mimicry, and transdifferentiation, in which tumor cells are pro-actively engaged. However, these neo-generated vascular networks are morphologically and functionally abnormal, suggesting that the vascularization processes are rather inefficient in the tumor ecosystem. In this review, we reiterate the specificities of each neovascularization modality in glioblastoma, and, how they can be hampered mechanistically in the perspective of anti-cancer therapies.

ATX-101, a Peptide Targeting PCNA, Has Antitumor Efficacy Alone or in Combination with Radiotherapy in Murine Models of Human Glioblastoma

“…Glioblastoma multiforme (GBM) is a very aggressive brain tumor [ 1 ] characterized by high inter- and intratumor heterogeneity [ 2 ] with high local invasiveness [ 3 ], extensive necrosis [ 4 ], and high vascularity [ 5 ]. Current standard treatments for this neoplasm include surgical resection combined with radiotherapy (RT) and chemotherapy [ 6 ].…”

SLUG and Truncated TAL1 Reduce Glioblastoma Stem Cell Growth Downstream of Notch1 and Define Distinct Vascular Subpopulations in Glioblastoma Multiforme

“…As for SLUG, combined FISH-immunofluorescence showed that TAL1 is present in few GBM EGFR-amplified tumoral cells. Considering that TAL1 is involved in endothelial differentiation during development and controls active angiogenesis in later stages, it is tempting to speculate that these TAL1 + GBM cells are endothelial-like cells, which have been previously described [ 81 , 82 ] and would result from a trans-differentiation of GBM cells [ 70 , 71 ]. Additional work is needed to establish the identity of these TAL1 + GBM cells, their contribution to GBM progression, and if they potentially participate in neovascularization processes.…”

“…This dual tumoral vs. non tumoral expression of SLUG was also observed at the RNA level, using one recent glioblastoma RNA seq database ( Figure S5E ) [ 48 ]. Due to technical limitations, we did not fully demonstrate that these SLUG + tumoral cells also co-expressed smooth muscle markers and adopted a pericyte-like phenotype as a result of a GBM-vascular trans-differentiation process [ 70 , 71 , 72 ]. More work using new multiplexing approaches would be necessary to address this issue and assess the contribution of SLUG + GBM cells to GBM progression and, potentially, to neovascularization mechanisms.…”

Glioblastoma Microenvironment and Cellular Interactions

“…In the third place, the identification of different subsets of GSCs represents another controversial point. The GSCs are characterized by sustained self-renewal, persistent proliferation, tumor initiation, frequency within a GBM tumor, marker expression, ability to generate progeny of multiple lineages, and chemo/radio resistance [ 169 , 179 , 180 ]. There is no consensus for the surface markers used for identifying the GSCs, which are constantly updated [ 181 ].…”