Description:

The Department of Biochemistry and Molecular Genetics presents:

Alexander Muir, Assistant Professor, Ben May Department of Cancer Research University of Chicago

Title: "What is There to Eat Around Here? How the Tumor Nutrient Microenvironment Impacts Cancer Metabolism and Therapy Response"

Abstract:

Cancer metabolism is influenced both by cell-intrinsic factors and cell-extrinsic factors. There has been substantial effort to understand how cell-intrinsic factors, such as oncogenic lesions, alter cellular metabolism. However, much less is known about how microenvironmental conditions alter cancer metabolism. Nutrient availability is a cell-extrinsic factor that substantially influences cellular metabolism, yet we have relatively little information regarding nutrient availability in tumors and how this impacts cancer metabolism. To address this, we developed a quantitative metabolomics approach to measure nutrient levels in the interstitial fluid (IF) of tumors, providing insight into the metabolic substrates available to cells in their local microenvironment. To determine how local nutrient availability alters cancer cell metabolism, we have developed a cell culture medium based on observed IF nutrient levels in murine pancreatic cancers. Pancreatic cancer cells, as well tumor stromal cells, can be grown in this IF-based medium to study how cells utilize metabolism to support homeostasis and function when constrained by microenvironmental nutrient levels. I will discuss metabolic adaptations that pancreatic cancer cells require to grow under such microenvironmental nutrient constraints that we have identified using this approach, and how these adaptations impact cancer cell response to therapeutics. In conclusion, we provide new tools determine how nutrient availability impacts cancer cell biology, metabolism and response to therapeutic interventions.