Metabolic alterations in lung cancer-associated fibroblasts correlated with increased glycolytic metabolism of the tumor

Virendra K. Chaudhri, Gregory G. Salzler, Salihah A. Dick, Melanie S. Buckman, Raffaella Sordella, Edward D. Karoly, Robert Mohney, Brendon M. Stiles, Olivier Elemento, Nasser K. Altorki, Timothy E. McGraw

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Cancer cells undergo a metabolic reprogramming but little is known about metabolic alterations of other cells within tumors. We use mass spectrometry - based profiling and a metabolic pathway - based systems analysis to compare 21 primary human lung cancer - associated fibroblast lines (CAF) to "normal" fibroblast lines (NF) generated from adjacent nonneoplastic lung tissue. CAFs are protumorigenic, although the mechanisms by which CAFs support tumors have not been elucidated. We have identified several pathways whose metabolite abundance globally distinguished CAFs from NFs, suggesting that metabolic alterations are not limited to cancer cells. In addition, we found metabolic differences between CAFs from high and low glycolytic tumors that might reflect distinct roles of CAFs related to the tumor's glycolytic capacity. One such change was an increase of dipeptides in CAFs. Dipeptides primarily arise from the breakdown of proteins. We found in CAFs an increase in basal macroautophagy which likely accounts for the increase in dipeptides. Furthermore, we show a difference between CAFs and NFs in the induction of autophagy promoted by reduced glucose. In sum, our data suggest that increased autophagy may account for metabolic differences between CAFs and NFs and may play additional as yet undetermined roles in lung cancer.

Original languageEnglish (US)
Pages (from-to)579-592
Number of pages14
JournalMolecular Cancer Research
Volume11
Issue number6
DOIs
StatePublished - Jun 2013
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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