Multi-omics evaluation of cell lines as models for metastatic prostate cancer

Cancer cell lines are indispensable for prostate cancer research, yet their ability to model metastatic prostate cancer remains insufficiently characterized. In this study, we performed a systematic multi-omics evaluation integrating genomic and transcriptomic data from large public datasets. We identified VCaP as the most representative model for metastatic prostate adenocarcinoma, while highlighting the limited fidelity of the widely used PC3 cell line. Our analysis underscores the importance of selecting hypermutated cell lines, which display distinct tumor microenvironment characteristics. Moreover, overexpression of MET in VCaP induced partial stem-like traits but did not fully recapitulate the MSPC transcriptomic profile. Notably, stem-like prostate organoids demonstrated higher similarity to MSPC and may serve as more suitable MSPC models. Our study provides guidance for the selection of prostate cancer cell lines, assisting researchers in choosing more representative metastatic prostate cancer cell line models.