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SUMMARY:Role of Extracellular Metabolites in Tumor Organization - Dr Carlo
 s Carmona-Fontaine (Memorial Sloan Kettering Cancer Center)
DTSTART:20150422T120000Z
DTEND:20150422T130000Z
UID:TALK59169@talks.cam.ac.uk
CONTACT:Neil Bennett
DESCRIPTION:The microenvironment experienced by cancer cells plays a funda
 mental role in their tumorigenicity. Understanding how tumor cells integra
 te different external signals is necessary to predict and eventually contr
 ol cancer progression. Our work seeks to unravel how metabolic features of
  the microenvironment\, such as low pH and nutrient scarcity\, interact wi
 th cell communication to determine tumor growth. We will focus on the extr
 acellular impact of the deranged metabolism of cancer cells. We will show 
 that secretion and consumption of nutrients\, together with poor blood per
 fusion\, lead to spontaneous gradients of metabolites. These gradients can
  restrict the localization of stromal cells and they can become a source o
 f non-genetic intratumoral heterogeneity. This is because spontaneous grad
 ients of oxygen and lactate exert dramatic changes in the polarization sta
 te of Tumor-Associated Macrophages (TAMs). These metabolically-polarized T
 AMs are arranged in specific tumor regions and secrete particular sets of 
 cell signals. These signals in turn\, can modulate the behavior of neighbo
 ring cells and thus effectively amplify the effect of metabolic gradients.
  We will also discuss how cooperation among cancer cells makes them more r
 esilient to the effect of disturbed microenvironments. In summary\, we pro
 pose that gradients of extracellular metabolites are drivers of phenotypic
  intratumoral heterogeneity\, a common tumor feature that hampers effectiv
 e diagnosis and treatment.
LOCATION:Cancer Research UK Cambridge Institute\, Lecture Theatre
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