Figure 5. Cancer cell metabolism influences the tumor microenvironment and can support metastasis formation.

Cell types are indicated with respect to their location in the tumor microenvironment (labeled in the bottom edge), plus nutrients that have been shown to influence their activity in vivo. (A) The mechanistic consequences of tumor detachment and response to doxorubicin therapy can drive gene expression changes regulating nutrient utilization in circulating tumor cells. Abbreviations: Doxorubicin (DOX), GSH (glutathione), FAO (fatty acid oxidation), ROS (reactive oxygen species). (B) Immunoregulatory interactions can be elicited by metabolic byproducts of the intratumoral metabolism, which can act as immune regulators in the metastatic niche. (C) Nutrients can influence metastatic seeding and outgrowth by modulating immune responses and effector functions. Abbreviations: TCA (Tricarboxylic acid cycle), mTOR (mammalian target of rapamycin).