Role of Extracellular Metabolites in Tumor Organization

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• Dr Carlos Carmona-Fontaine (Memorial Sloan Kettering Cancer Center)
• Wednesday 22 April 2015, 13:00-14:00
• Cancer Research UK Cambridge Institute, Lecture Theatre.

If you have a question about this talk, please contact Neil Bennett.

The microenvironment experienced by cancer cells plays a fundamental role in their tumorigenicity. Understanding how tumor cells integrate different external signals is necessary to predict and eventually control cancer progression. Our work seeks to unravel how metabolic features of the microenvironment, such as low pH and nutrient scarcity, interact with cell communication to determine tumor growth. We will focus on the extracellular impact of the deranged metabolism of cancer cells. We will show that secretion and consumption of nutrients, together with poor blood perfusion, lead to spontaneous gradients of metabolites. These gradients can restrict the localization of stromal cells and they can become a source of non-genetic intratumoral heterogeneity. This is because spontaneous gradients of oxygen and lactate exert dramatic changes in the polarization state of Tumor-Associated Macrophages (TAMs). These metabolically-polarized TAMs are arranged in specific tumor regions and secrete particular sets of cell signals. These signals in turn, can modulate the behavior of neighboring cells and thus effectively amplify the effect of metabolic gradients. We will also discuss how cooperation among cancer cells makes them more resilient to the effect of disturbed microenvironments. In summary, we propose that gradients of extracellular metabolites are drivers of phenotypic intratumoral heterogeneity, a common tumor feature that hampers effective diagnosis and treatment.

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