Extracellular Matrix-Bound FGF2 Mediates Estrogen Receptor Signaling and Therapeutic Response in Breast Cancer.

ABSTRACT: The extracellular matrix (ECM) is often unaccounted for in studies that consider the stromal contribution to cancer cell signaling and response to treatment. To investigate the influence of a fibrotic microenvironment, we use fibroblast-derived ECM scaffolds as a cell culture platform. We uncover that estrogen receptor-positive (ER⁺) breast cancer cells cultured within ECM-scaffolds have an increase in ER signaling that occurs via an MAPK-dependent, but estrogen-independent manner. The ECM acts as a reservoir by binding, enriching, and presenting growth factors to adjacent epithelial cells. We identified FGF2 as a specific ECM-bound factor that drives ER signaling. ER⁺ cells cultured on ECM matrices have reduced sensitivity to ER-targeted therapies. The sensitivity to

SUBMITTER: DiGiacomo JW 

PROVIDER: S-EPMC7785668 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature