The authors suggest that vascular remodeling takes place and a more hypoxic tumor microenvironment predominates in the tumor model 28.
Moreover, the administration of antiangiogenic agents, particularly antibodies against VEGF, leads to a more hypoxic tumor microenvironment [ 31], which enhances tumor cell invasion and metastasis by inducing the EMT- and CSC-like phenotype [ 32– 32].
The use of CHO engineered cells, which apparently are more resistant than LM to the hypoxic microenvironment of the immunoisolation devices is other alternative to keep endostatin serum levels.
Thus, the microenvironment of a tumour is generally more hypoxic (Mekhail et al, 2004; Kapitsinou and Haase, 2008; Vaupel, 2008) and acidic than normal tissues.
However, more recently, the study of gene expression regulated by a hypoxic microenvironment has become a focus of intense research.
Multicellular spheroids that model the hypoxic microenvironment in vivo can be exploited to achieve a more comprehensive assessment of factors contributing to resistance of hypoxic cells within tumours (Jones et al, 1982; West et al, 1984; Olive et al, 1996).
In this study, we reprogrammed primary Glioblastoma multiforme (GBM -derived cells towards a more differentiated and less oncoGBM -derivedype by acellstowardse Wnt pathway in a hypoxic moreoenvironment.
That said, our data are in agreement with the function of Wnts having a more prevalent role as pro-differentiation factors, at least under conditions that recapitulate the physiological hypoxic microenvironment of the brain.
Hence, we should take non-CSCs and the hypoxic microenvironment into consideration when developing tumor treatments.
The hypoxic microenvironment maintains glioblastoma stem cells and promotes reprogramming towards a cancer stem cell phenotype.
