Experimental models of histogenesis and tumor cell heterogeneity in bladder cancer

The histogenetic relationships between the subtypes of bladder cancer are not known. Each common pattern (transitional cell carcinoma, adenocarcinoma, and squamous carcinoma) can exist independently, although they may coexist in primary or metastatic bladder cancers, and tumors that are predominantly composed of transitional cell carcinoma may have regions of squamous or glandular differentiation. Morphologically identical tumors exhibit marked variation in their natural history and response to treatment. To study these aspects of the biology of human bladder cancer, a series of cell lines have been established and characterized as xenografts and in tissue culture. These studies have shown a likely common origin for transitional cell carcinoma, adenocarcinoma, and squamous carcinoma of the bladder. Morphologically similar xenografts and cell lines in vitro have shown a broad range of functional heterogeneity, including ultrastructure, tumor marker production, ploidy, cell surface characteristics, and response to chemotherapy. These are useful models of heterogeneity of response to treatment with established and new cytotoxic agents.