Pathophysiological Integration of Metabolic Reprogramming in Breast Cancer

SIMPLE SUMMARY: Tumors exhibit metabolic changes that differentiate them from the normal tissues from which they derive. These metabolic changes favor tumor growth, are primarily induced by cancer cells, and produce metabolic and functional changes in the surrounding stromal cells. There is a close functional connection between the metabolic changes in tumor cells and those that appear in the surrounding stroma. A better understanding of intratumoral metabolic interactions may help identify new vulnerabilities that will facilitate new, more individualized treatment strategies against cancer. We review the metabolic changes described in tumor and stromal cells and their functional changes and then consider, in depth, the metabolic interactions between the cells of the two compartments. Although these changes are generic, we illustrate them mainly with reference to examples in breast cancer. ABSTRACT: Metabolic changes that facilitate tumor growth are one of the hallmarks of cancer. The triggers of these metabolic changes are located in the tumor parenchymal cells, where oncogenic mutations induce an imperative need to proliferate and cause tumor initiation and progression. Cancer cells undergo significant metabolic reorganization during disease progression that is tailored to their energy demands and fluctuating environmental conditions. Oxidative stress plays an essential role as a trigger under such conditions. These metabolic changes are the consequence of the interaction between tumor cells and stromal myofibroblasts. The metabolic changes in tumor cells include protein anabolism and the synthesis of cell membranes and nucleic acids, which all facilitate cell proliferation. They are linked to catabolism and autophagy in stromal myofibroblasts, causing the release of nutrients for the cells of the tumor parenchyma. Metabolic changes lead to an interstitium deficient in nutrients, such as glucose and amino acids, and acidification by lactic acid. Together with hypoxia, they produce functional changes in other cells of the tumor stroma, such as many immune subpopulations and endothelial cells, which lead to tumor growth. Thus, immune cells favor tissue growth through changes in immunosuppression. This review considers some of the metabolic changes described in breast cancer.