Age-associated microenvironmental changes highlight the role of PDGF-C in ER⁺ breast cancer metastatic relapse.

ABSTRACT: Patients with estrogen receptor (ER)-positive breast cancer are at risk of metastatic relapse for decades after primary tumor resection and treatment, a consequence of dormant disseminated tumor cells (DTCs) reawakening at secondary sites. Here we use syngeneic ER⁺ mouse models in which DTCs display a dormant phenotype in young mice but accelerated metastatic outgrowth in an aged or fibrotic microenvironment. In young mice, low-level Pdgfc expression by ER⁺ DTCs is required for their maintenance in secondary sites but is insufficient to support development of macrometastases. By contrast, the platelet-derived growth factor (PDGF)-C^hi environment of aging or fibrotic lungs promotes DTC proliferation and upregulates tumor cell Pdgfc expression stimulating fur

SUBMITTER: Turrell FK 

PROVIDER: S-EPMC10132974 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature