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Intratumor Heterogeneity in Primary Kidney Cancer Revealed by Metabolic Profiling of Multiple Spatially Separated Samples within Tumors.

Abstract：

:Metabolic alteration constitutes a hallmark of cancer. Glycolysis and antioxidant pathways in kidney cancer are elevated, with frequent mutation of the VHL gene. Intratumor genetic heterogeneity has been recently demonstrated in kidney cancer. However, intratumor metabolic heterogeneity has not been investigated. Here, we used global metabolomics analysis and tissue slice tracer studies to demonstrate that different portions of a human primary kidney tumor possess different metabolic characteristics and drug sensitivity. Pyruvate levels were elevated and pyruvate metabolism was altered in some tumor sections. These observations indicated that pyruvate metabolism may constitute a possible vulnerability of kidney cancer; indeed, pyruvate stimulated the growth of primary kidney cancer cells and pharmacological inhibition of pyruvate transporters slowed the growth of patient-derived kidney tumors in mice. These findings deepen our understanding of the intratumor metabolic heterogeneity of kidney cancer and may inform novel therapeutic approaches in human kidney cancer.

journal_name

EBioMedicine

journal_title

EBioMedicine

authors

Okegawa T,Morimoto M,Nishizawa S,Kitazawa S,Honda K,Araki H,Tamura T,Ando A,Satomi Y,Nutahara K,Hara T

doi

10.1016/j.ebiom.2017.04.009

subject

Has Abstract

pub_date

2017-05-01 00:00:00

pages

31-38

issn

2352-3964

pii

S2352-3964(17)30152-4

journal_volume

19

pub_type

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