Establishing the first Afro-Caribbean breast cancer cell lines reveals ECM pathway enrichment and distinctive drug sensitivities

Women of African ancestry develop more aggressive breast cancer (BCa) with poorer survival outcomes, yet only 8% of available cell lines represent this population, impeding targeted treatment development. Here, we aimed to establish and characterize new cell lines from an Afro-Caribbean patient to better understand population-specific BCa biology. We developed three lines (ACRJ-BC24 parent, α, and β) from a patient with 100% African ancestry. Karyotype analysis revealed progressive chromosomal instability, with the β-clone showing X-11 translocations correlating with higher Ki-67 expression and enhanced tumorigenic capacity. Immunohistochemistry and immunoblotting demonstrated their transition from hormone-positive to triple-negative phenotypes. Transcriptional profiling identified significant enrichment in extracellular matrix organization pathways mechanistically linked to chromosomal instability, explaining their distinct drug responses. The parent line demonstrated notable sensitivity to PARP inhibitors and microtubule-targeting agents, while the β-clone showed enhanced platinum sensitivity correlating with its chromosomal abnormalities. The parent line exhibited atypical dose-response patterns to gemcitabine and docetaxel, possibly relating to ECM-mediated drug transport mechanisms. This resource provides valuable tools for studying BCa disparities in African ancestry populations, offering the first cell line models from this underrepresented population for hypothesis-driven mechanistic studies.