Bone Marrow Mesenchymal Stem Cells Induce Metabolic Plasticity in Estrogen Receptor-Positive Breast Cancer.

ABSTRACT: Cancer cells reprogram energy metabolism through metabolic plasticity, adapting ATP-generating pathways in response to treatment or microenvironmental changes. Such adaptations enable cancer cells to resist standard therapy. We employed a coculture model of estrogen receptor-positive (ER+) breast cancer and mesenchymal stem cells (MSC) to model interactions of cancer cells with stromal microenvironments. Using single-cell endogenous and engineered biosensors for cellular metabolism, coculture with MSCs increased oxidative phosphorylation, intracellular ATP, and resistance of cancer cells to standard therapies. Cocultured cancer cells had increased MCT4, a lactate transporter, and were sensitive to the MCT1/4 inhibitor syrosingopine. Combining syrosingopine with fulvestrant, a selective est

SUBMITTER: Buschhaus JM 

PROVIDER: S-EPMC10159984 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature