Chaudhri V K, et al., Metabolic Alterations in Lung Cancer-Associated Fibroblasts Correlated with Increased Glycolytic Metabolism of the Tumor. Molecular Cancer Research, 2013. 11(579-592.
Metabolon results led to:
- That autophagy is a distinguishing feature of cancer associated fibroblasts (CAFs)
- Greater understanding of the tumor microenvironment
- A template for how to investigate tumor metabolism in its isolated parts (i.e. stroma vs. epithelium)
Key metabolomic observations:
- Marker of protein breakdown (dipeptides) were increased in CAFs
There is significant appreciation that cancer cells undergo metabolic reprogramming but there is far less understanding of the metabolic phenotypes of the other cell types comprising the ”ecosystem” of the microenvironment. As a first step, investigators sought to derive the metabolic profile of primary human lung tumor cancer-associated fibroblast lines (CAFs) compared to “normal” fibroblast lines (NFs) generated from adjacent non-neoplastic lung tissue. Dipeptides were the clearest signature segregating the CAFs from the most glycolytic tumors and led to the hypothesis that CAFs may engage autophagy more than NFs. Follow-up experiments confirmed this hypothesis. These distinctions in metabolic features in the cells comprising the microenvironment may also assist in devising next generation combination therapies that target aspects of both the cancer cell and the stroma.