HT-1376

The HT-1376 cell line is a widely utilized human bladder cancer line established from a high-grade (grade 3) primary transitional cell carcinoma (urothelial carcinoma) of a 58-year-old female patient. Because it originates from an untreated primary muscle-invasive tumor, HT-1376 faithfully captures the molecular and biological hallmarks of aggressive bladder cancer without the genomic confounders of prior chemotherapy.

A defining advantage of HT-1376 is its well-characterized p53 pathway deficiency. The cells harbor a homozygous missense mutation in TP53 at codon 245 (G245D), a classic gain-of-function hotspot mutation that abrogates wild-type tumor-suppressor activity and drives genomic instability. This provides a consistent and clinically relevant genetic background for investigating p53-driven tumorigenesis and drug resistance. Phenotypically, HT-1376 cells grow as an adherent monolayer with typical epithelial cobblestone morphology and robustly express urothelial keratins (CK7, CK8, CK18, CK19), confirming lineage fidelity. When implanted subcutaneously into immunodeficient mice, they reliably form moderately differentiated xenograft tumors that recapitulate the infiltrative histology of human muscle-invasive bladder cancer, including stromal invasion.

The combination of a stable epithelial phenotype, precisely defined TP53 mutation, and reproducible in vivo tumorigenicity makes HT-1376 an indispensable platform for dissecting the molecular mechanisms of bladder cancer invasion, evaluating platinum-based and targeted therapeutics, and studying epithelial-mesenchymal transition. Its origin from a primary lesion, rather than a metastatic site, further enhances its relevance as a model for early-stage invasive bladder cancer research.