(173c) Lactate's Impact on Breast Cancer Metabolism

Long recognized as an important metabolic by-product in cell culture processes, lactate has also recently been discovered to promote malignant behavior in breast cancer cells. Lactate can accumulate in poorly vascularized tumors and is associated with cancer stem cell-like gene activity, drug resistance, metastasis, and poor prognosis in breast cancer patients. Unfortunately, little is known about how lactate affects cell behavior at the metabolic pathway level as breast cancer progresses. To that end, this study employed steady-state metabolic flux analysis to examine the metabolic activity of normal breast cells (MCF10A), early stage breast cancer cells (MCF7), and advanced, malignant breast cancer cells (MDA-MB-231) in response to cultures with high lactate levels versus control conditions. Flux maps were constructed based on growth rate data, consumption rates of nutrients and amino acids, and mass isotopomer distribution obtained from three parallel isotopic tracer experiments - glucose, glutamine, and lactate - each conducted in triplicate. The cell metabolism at different stages of breast cancer resulted in different responses to high lactate levels. The implication of these findings towards better diagnostic and therapeutic techniques will be discussed.