Understanding the Metabolic Cross Talk Between Cancer Cells and Cancer-Associated Fibroblasts

The tumor microenvironment (TME) is a heterogeneous, complex, and dynamic setting in which both invading tumor and local stromal cells reside, coevolve, and form a metabolic symbiosis that dictates downstream steps of cancer development and progression. Besides tumor cells, cancer-associated fibroblasts (CAFs) are the predominant cell type found in the majority of solid tumor microenvironment. It is recognized that cancer cells induce a metabolic phenotype in CAFs that is conducive to cancer progression. In addition, CAFs produce nutrients and metabolites, which are utilized by the tumor for energy production, proliferation, invasion, and migration. However, the precise mechanisms whereby CAFs contribute to the process remain uncertain. CAFs are believed to contribute to tumor metabolism through the production of high energy intermediates to fuel glycolytic, oxidative, amino acid, and fatty acid metabolism of cancer cells. This chapter consolidates recent findings regarding the metabolic cross talk occurring between CAFs and cancer cells within the tumor microenvironment.