Metabolic Alterations in Lung Cancer-Associated Fibroblasts Correlated with Increased Glycolytic Metabolism of the Tumor

Chaudhri, V. K., Salzler, G. G., Dick, S. A., Buckman, M. S., Sordella, R., Karoly, E. D., Mohney, R., Stiles, B. M., Elemento, O., Altorki, N. K., McGraw, T. E. (June 2013) Metabolic Alterations in Lung Cancer-Associated Fibroblasts Correlated with Increased Glycolytic Metabolism of the Tumor. Molecular Cancer Research, 11 (6). pp. 579-592. ISSN 1541-7786

DOI: 10.1158/1541-7786.mcr-12-0437-t


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. (C)2013 AACR.

Item Type: Paper
Uncontrolled Keywords: autophagy microenvironment growth trafficking activation carcinoma survival cells
Subjects: diseases & disorders > cancer
diseases & disorders
diseases & disorders > cancer > cancer types > lung cancer
organs, tissues, organelles, cell types and functions > organs types and functions > metabolism
CSHL Authors:
Communities: CSHL labs > Sordella lab
CSHL Cancer Center Program > Signal Transduction
Depositing User: Matt Covey
Date: June 2013
Date Deposited: 19 Jul 2013 16:09
Last Modified: 15 Oct 2015 20:04
PMCID: PMC3686965
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