436637 Understanding Tumor Microenvironment's Metabolic Regulation of Cancer Cells

Wednesday, November 11, 2015: 2:42 PM
155A (Salt Palace Convention Center)
Deepak Nagrath, Department of Chemical Engineering, Rice University, Houston, TX and Lifeng Yang, Rice University, Houston, TX

Tumor cells need appropriate nutrient for growth, invasion and energy metabolism. A growing number of studies indicate that metabolic dependencies of cancer cells are regulated by tumor microenvironment (TME) which rewires the cellular metabolism to promote tumorigenicity. Glutamine can play a critical role in cellular growth in multiple cancers. Recently, we uncovered a missing link between cancer invasiveness and glutamine dependence. Using isotope tracer and bioenergetic analysis, we showed that low‐invasive ovarian cancer (OVCA) cells are glutamine independent, whereas high‐invasive OVCA cells are markedly glutamine dependent. Here, we present a multidimensional approach, where we synergistically integrate in vitro stable isotope metabolomics, cell functional assays (invasion, migration, proliferation, 3D cocultures), mitochondrial bioenergetics, clinicopathological features (patient derived CAFs and stromal fibroblasts, and patient derived cancer cells), targeted therapies using in culture and in vivo models, to understand TME regulation of OVCA growth and metastasis. We will demonstrate a novel mechanism by which stromal cancer associated fibroblasts cells maintain tumor growth in OVCA cells.

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