@article {3132786,
	title = {Intra-Tumoral Metabolic Zonation and Resultant Phenotypic Diversification Are Dictated by Blood Vessel Proximity},
	journal = {Cell Metab},
	volume = {30},
	number = {1},
	year = {2019},
	note = {Kumar, SaranSharife, HusniKreisel, TirzahMogilevsky, MaximBar-Lev, LibatGrunewald, MyriamAizenshtein, ElinaKarni, RotemPaldor, IddoShlomi, TomerKeshet, EliengResearch Support, Non-U.S. Gov{\textquoteright}tCell Metab. 2019 Jul 2;30(1):201-211.e6. doi: 10.1016/j.cmet.2019.04.003. Epub 2019 May 2.},
	month = {Jul 2},
	pages = {201-211 e6},
	edition = {2019/05/06},
	abstract = {Differential exposure of tumor cells to blood-borne and angiocrine factors results in diverse metabolic microenvironments conducive for non-genetic tumor cell diversification. Here, we harnessed a methodology for retrospective sorting of fully functional, stroma-free cancer cells solely on the basis of their relative distance from blood vessels (BVs) to unveil the whole spectrum of genes, metabolites, and biological traits impacted by BV proximity. In both grafted mouse tumors and natural human glioblastoma (GBM), mTOR activity was confined to few cell layers from the nearest perfused vessel. Cancer cells within this perivascular tier are distinguished by intense anabolic metabolism and defy the Warburg principle through exercising extensive oxidative phosphorylation. Functional traits acquired by perivascular cancer cells, namely, enhanced tumorigenicity, superior migratory or invasive capabilities, and, unexpectedly, exceptional chemo- and radioresistance, are all mTOR dependent. Taken together, the study revealed a previously unappreciated graded metabolic zonation directly impacting the acquisition of multiple aggressive tumor traits.},
	keywords = {*blood vessels, *Glioblastoma, *metabolic compartmentalization, *mTOR pathway, *tumor heterogeneity, *tumor microenvironment, *tumor vasculature, Animals, Apoptosis/physiology, Blood Vessels/metabolism, Cell Line, Tumor, Cell Movement/physiology, Cell Proliferation/physiology, Cell Size, Cell Survival/physiology, Flow Cytometry, Glioblastoma/*metabolism, Humans, immunoblotting, Male, Metabolomics/*methods, Mice, Mice, SCID, Mitochondria/metabolism, Oxygen Consumption/physiology, Principal Component Analysis},
	isbn = {1932-7420 (Electronic)1550-4131 (Linking)},
	url = {https://pubmed.ncbi.nlm.nih.gov/31056286},
	author = {Kumar, S. and Sharife, H. and Kreisel, T. and Mogilevsky, M. and Bar-Lev, L. and Grunewald, M. and Aizenshtein, E. and Karni, R. and Paldor, I. and Shlomi, T. and Keshet, E.}
}
