Mechanical and metabolic interplay in the brain metastatic microenvironment - Onwudiwe, Killian; Burchett, Alice A.; Datta, Meenal (Frontiers in Oncology, 2022)
In this Perspective, we provide our insights and opinions about the contribution – and potential co-regulation – of mechanics and metabolism in incurable breast cancer brain metastasis. Altered metabolic activity can affect cancer metastasis, as high glucose supply and demand in the brain microenvironment favors aerobic glycolysis. Similarly, the altered mechanical properties of disseminating cancer cells facilitate migration to and metastatic seeding of the brain, where local metabolites support their progression. Cancer cells in the brain and the brain tumor microenvironment often possess opposing mechanical and metabolic properties compared to extracranial cancer cells and their microenvironment, which inhibits the ease of extravasation and metastasis of these cells outside of the central nervous system. We posit that the brain provides a metabolic microenvironment that mechanically reinforces the cellular structure of cancer cells and supports their metastatic growth while restricting its spread from the brain to external organs.