The metabolic crosstalk of cancer-associated fibroblasts and tumor cells: Recent advances and future perspectives.

Tumor cells grow in a microenvironment with a lack of nutrients and oxygen. Cancer-associated fibroblasts (CAFs) as one major component of tumor microenvironment have strong ability to survive under stressful conditions through metabolic remodelling. Furthermore, CAFs are educated by tumor cells and help them adapt to the hostile microenvironment through their metabolic communication. By inducing catabolism, CAFs release nutrients into the microenvironment which are taken up by tumor cells to satisfy their metabolic requirements. Furthermore, CAFs can recycle toxic metabolic wastes produced by cancer cells into energetic substances, allowing cancer cells to undergo biosynthesis. Their metabolic crosstalk also enhances CAFs' pro-tumor phenotype and reshape the microenvironment facilitating tumor cells' metastasis and immune escape. In this review, we have analyzed the effect and mechanisms of metabolic crosstalk between tumor cells and CAFs. We also analyzed the future perspectives in this area from the points of CAFs heterogeneity, spatial metabonomics and patient-derived tumor organoids (PDOs). These information may deepen the knowledge of tumor metabolism regulated by CAFs and provide novel insights into the development of metabolism-based anti-cancer strategies.