@entity1 pancreatic cancer tumors are nutrient poor and XXXX cells actively scavenge extracellular protein.

@entity1 @entity1124 @entity984 @entity5 @entity19
Glucose and amino acids are key nutrients supporting cell growth. Amino acids are imported as monomers, but an alternative route induced by oncogenic @entity984 involves uptake of extracellular proteins via macropinocytosis and subsequent lysosomal degradation of these proteins as a source of amino acids. In this study, we examined the metabolism of @entity1124 ( @entity1124 ), a poorly vascularized lethal @entity984 -driven malignancy. Metabolomic comparisons of @entity1 @entity1124 and benign adjacent tissue revealed that @entity5 tissue was low in glucose, upper glycolytic intermediates, creatine phosphate, and the amino acids glutamine and serine, two major metabolic substrates. Surprisingly, @entity1124 accumulated essential amino acids. Such accumulation could arise from extracellular proteins being degraded through macropinocytosis in quantities necessary to meet glutamine requirements, which in turn produces excess of most other amino acids. Consistent with this hypothesis, active macropinocytosis is observed in primary @entity1 @entity1124 specimens. Moreover, in the presence of physiologic albumin, we found that cultured @entity19 @entity1124 cells grow indefinitely in media lacking single essential amino acids and replicate once in the absence of free amino acids. Growth under these conditions was characterized by simultaneous glutamine depletion and essential amino acid accumulation. Overall, our findings argue that the scavenging of extracellular proteins is an important mode of nutrient uptake in @entity1124 . @entity5 Res; 75(3); 544-53.   2014 AACR.
