Cancer cell proliferation is often nutrient limited, especially before vascularization of the growing tumor (i.e. angiogenesis).  We hypothesize that during the early stages of tumor formation cancer cells obtain nutrients by cannibalizing neighboring cells and/or extracellular matrix proteins. To investigate this concept, tumor formation has been recapitulated in culture dishes using transformed h293 cells. They override contact inhibitory pathways and grow on top of one another to form foci, which are like small tumors.  Nutrient conditions for foci formation have been examined by manipulating glucose and glutamine levels in the culture media. In addition, the involvement of these metabolic pathways in cell proliferation and foci formation have been investigated using specific inhibitors of glycolysis and glutaminolysis. H293 cells were still able to form foci in the absence of nutrients generally considered essential, which may reflect a means to preserve cell viability through the sharing of nutrients or through the cannibalism of internal cells.  In fact, cells under inhibitory conditions appeared to form foci at a more rapid rate, raising the interesting possibility that cells are obtaining and using metabolites more efficiently under nutrient deprived conditions.

Nutrient requirements for foci formation of cancer cells

247th National Meeting (2014)

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