Intratumor Heterogeneity in Primary Kidney Cancer Revealed by Metabolic Profiling
of Multiple Spatially Separated Samples within Tumors
#MMPMID28408240
Okegawa T
; Morimoto M
; Nishizawa S
; Kitazawa S
; Honda K
; Araki H
; Tamura T
; Ando A
; Satomi Y
; Nutahara K
; Hara T
EBioMedicine
2017[May]; 19
(?): 31-38
PMID28408240
show ga
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.
|Acrylates/pharmacology
[MESH]
|Animals
[MESH]
|Antineoplastic Agents/therapeutic use
[MESH]
|Cells, Cultured
[MESH]
|Female
[MESH]
|Glycolysis
[MESH]
|Humans
[MESH]
|Kidney Neoplasms/drug therapy/*metabolism
[MESH]
|Metabolomics
[MESH]
|Mice
[MESH]
|Pyruvic Acid/*metabolism
[MESH]
|Sirolimus/analogs & derivatives/therapeutic use
[MESH]
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