Aged and BRCA-Mutated Stromal Cells Drive Epithelial Cell Transformation.

ABSTRACT: The fundamental steps in high-grade serous ovarian cancer (HGSOC) initiation are unclear, presenting critical barriers to the prevention and early detection of this deadly disease. Current models propose that fallopian tube epithelial (FTE) cells transform into serous tubal intraepithelial carcinoma (STIC) precursor lesions and subsequently into HGSOC. In this study, we report that an epigenetically altered mesenchymal stem cell niche, termed high-risk mesenchymal stromal/stem cell (hrMSC), exists prior to STIC lesion formation. hrMSCs are enriched in STIC stroma and contribute to a stromal "field effect" extending beyond the borders of the STIC lesion. hrMSCs promote DNA damage in FTE cells while also fostering FTE cell survival. hrMSCs induce malignant transformation of the FTE, resultin

SUBMITTER: Garcia GL 

PROVIDER: S-EPMC12130807 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature