Abstract 3381: Diversifying the breast cancer cell line repository with ACRJ-BC24, ACRJ-BC24α, and ACRJ-BC24β: Novel TNBC cell lines derived from an Afro-Caribbean patient

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Abstract Breast cancer is a leading global health burden; however, women of African ancestry are disproportionately affected and have an increased risk of developing more aggressive breast cancer, triple-negative breast cancer (TNBC), and consequently suffering poorer outcomes. One factor contributing to this cancer disparity is the lack of diverse representation in preclinical models and clinical trials. Cell lines are widely used preclinical models, though of the breast cancer cell lines commercially available, only 8% are derived from women of African ancestry, compared to 90% from women of European ancestry. Thus, diversifying cancer cell lines would better represent the population as a whole and strengthen the translatability of results. The aim of this study was to develop and characterize three novel breast cancer cell lines derived from a woman of African-Caribbean ancestry, ACRJ BC24 parent, ACRJ BC24α, and ACRJ BC24β. Characterization assays included cell line authentication, growth curve analysis, western blots, immunohistochemistry staining, flow cytometry, whole-genome sequencing (WGS), RNA-sequencing (RNA-seq), xenografts, and karyotyping. Short tandem repeat profiling confirmed the novelty and human origin of the cell line. WGS confirmed the cell lines to be of 100% African ancestry. The ACRJ-BC24 parent, α, and β lines have been passaged over 70 times in vitro with a doubling time of 70 hours, 133 hours, and 70 hours, respectively. All cell lines were confirmed triple-negative, CD49f+ and EpCAM-, as well as CD44+ and CD24-, suggesting a basal-like subtype. Additionally, all the ACRJ BC24 cell lines expressed vimentin but not E-Cadherin, suggesting a mesenchymal phenotype. Expression of N-cadherin is demonstrated in the parent and α line, but not in the β line, showing varying levels of epithelial-mesenchymal transition amongst the lines. Additionally, varying intensity of expression of CD49f was observed between the three ACRJ BC24 lines, further confirming a biological distinction. Cytotoxicity of 10 chemotherapy drugs was assessed against the 3 novel cell lines and established lines (MCF7, T47D, HCC70, and HCC1806). Differential viability was observed among the cell lines as gemcitabine and docetaxel were most potent against ACRJ BC24α with IC50s of 4.6 nM and 10 nM respectively compared to all other cell lines. Our findings confirm the need for increased representation of Black breast cancer cell lines among the preclinical panel for drug screens. The inclusion of these three novel Afro-Caribbean breast cancer cell lines in preclinical models will provide further insight into the current disparities among Black and White breast cancer cell lines. Citation Format: Isabella Allen, Shannique Clarke, Jovanka Ravix, Alex P. Sanchez Covarrubias, Ayodele Omotoso, Derria Cornwall, Sheray N. Chin, Sharon Harrison, Claude-Henry Claude-Henry Volmar, Shannon Saigh, Bilbao Cortes Bilbao Cortes, Elizabeth Smith, Rory Thompson, Camille Ragin, Sophia George, Simone Ann Marie Badal. Diversifying the breast cancer cell line repository with ACRJ-BC24, ACRJ-BC24α, and ACRJ-BC24β: Novel TNBC cell lines derived from an Afro-Caribbean patient [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3381.

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