CaB34 –a spontaneously immortalized prostate cancer cell line from a Black Caribbean patient, and its radioresistant subline, as novel research models

Prostate cancer cell lines are particularly racially and clinically homogenous, and while there has been significant work in the development of additional models, few have been created without oncogenic transformation. Here we describe the derivation of a spontaneously immortalized primary prostate cancer cell line from a Black Caribbean patient with Gleason 7 prostate cancer – designated CaB34 - which presents a novel model for pre-clinical study of localized prostate cancer. From CaB34, a paired radioresistant subline CaB34-CF was generated using a clinically relevant fractionated radiotherapy schedule. Both CaB34 and CaB34-CF express prostate-specific markers including CK18, NKX3.1, and AMACR. Multi-omic analyses using RNAseq and shotgun proteomics identified NNMT as the most significantly dysregulated target in CaB34-CF. Bioinformatic analysis determined that NNMT was more abundant within prostate tumors compared to benign prostate, supporting a role in tumor progression. Knockdown studies of NNMT demonstrated significant radiosensitization of both CaB34-CF cells, which was largely a result of increased radiation-induced cellular senescence. Our findings present NNMT as a potential therapeutic target for sensitization of radioresistant disease. Together, our research provides a paired model of treatment naive and radioresistant disease to address mechanisms of therapy resistance, while expanding the racial diversity of prostate cancer cell lines for the research community.