Figure 1. (A) A mechanism for reprograming of normal fibroblasts (FBs) into cancer-associated fibroblasts (CAFs) by cancer cells (CC) through secreted effectors.
These include cytokines and extracellular vesicles. The dashed arrow indicates a potential therapeutic intervention to normalize CAFs and the tumor microenvironment. The normal fibroblasts would no longer aid the cancer cells in their survival in adverse metabolic conditions. See also Fig. 11. (B) A conceptual model for the bidirectional Gln/NH4+ metabolism of both cancer cells and CAFs in monoculture. Both cell types are able to convert waste into nutrient, however the cancer cells decline in number when they have to do that. The combined populations show an improved temporary survival of cancer cells compared to the cancer cell monoculture.