Metabolism plays a critical role in the progression of cancer malignancy, with nutrient source flexibility allowing cancer cells to outcompete normal cells and survive harsh environmental conditions. Lactate, which accumulates in poorly vascularized tumors and was predominantly considered to be a waste product resulting from the Warburg Effect, is now believed to additionally serve as a metabolic substrate for cancer cells. Lactate accumulation is associated with cancer stem cell-like gene expression, drug-resistance, metastasis, and poor prognosis in breast cancer patients. Unfortunately, little is known about the role of lactate in cancer cell metabolism and progression. This study examined the impact of extracellular lactate on the metabolic activity of normal breast cells (MCF-10A), early stage breast cancer cells (MCF-7), and advanced, malignant breast cancer cells (MDA-MB-231) by utilizing steady-state <sup>13</sup>C-metabolic flux analysis. To quantify individual metabolic pathway activity, metabolic flux maps were constructed for each cell line for both control and high lactate conditions. The high lactate condition resulted in altered cell metabolism for each of the cell lines, including a decrease in glycolytic flux and an increase in reductive carboxylation of glutamine. Reductive carboxylation has previously been observed to increase under hypoxia; however, lactate’s effect on reductive carboxylation has not yet been reported. The implications of these findings towards understanding the tumor microenvironment will be discussed.

Impact of high extracellular lactate on breast cancer metabolism

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.