Tissue Engineered Models of Brain Tumors and Their Applications

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FIGURE 3.2

BBB of capillaries and ECM in the brain. The figure was partly generated

using Servier Medical Art, provided by Servier, licensed under a Creative

Commons Attribution 4.0 unported license.

populating tumor core and periphery resulting in the alteration of the fun-

damental transport mechanisms. SLC2A1, ABCG2, ABCB1, SLCO1A2, and

MFSD2A are some of the examples carriers with lowered expression in the

tumor core. Of the note, LRP-1 and, fenestration and permeability-associated

protein, PLVAP are overexpressed in GBM [107, 113, 114]. Moreover, mor-

phological abnormalities of endothelial cells are reported in the blood-tumor

barrier. Phenotype of endothelial cells presumes a flattened morphology with

an enlarged nucleus that has a boost in migration potential in contrast to

the cobblestone phenotype of a healthy state [115]. Besides, once quiescent

endothelial cells are activated by tumor cells, they undergo transcriptional re-

programming. Within this network, activated growth loops sustain and push

for angiogenesis [116, 117]. In GBM, pericytes play protective roles for the tu-

mor and contribute invasion process [118]. Associated with hyperdilated and

thin-walled blood vessels of GBM, CSC-derived pericyte coverage of blood ves-

sels determines prognosis, as high pericyte coverage in GBM establishes low

patient survival. Results of ablation of these pericytes manifest as increased

vascular permeability and chemotherapeutic efficiency of etoposide [119].