CONSTITUTIVE PRODUCTION OF MULTIPLE CYTOKINES AND A HUMAN CHORIONIC-GONADOTROPIN BETA-SUBUNIT BY A HUMAN BLADDER-CANCER CELL-LINE (KU-19-19) - POSSIBLE DEMONSTRATION OF TOTIPOTENTIAL DIFFERENTIATION

Bladder cancer cells have been shown to secrete a variety of factors t hat are not related to cells of urothelial origin. The histogenesis of these tumour developments is uncertain, and a variety of theories hav e been previously reported. In the present manuscript, we identify the factors constitutively produced by a human bladder cancer cell line ( KU-19-19) that was found to produce beta human chorionic gonadotrophin (beta-hCG), granulocyte colony-stimulating factor (G-CSF), granulocyt e-macrophage colony-stimulating factor (GMCSF), interleukin 1 alpha (I L-1 alpha), interleukin 6 (IL-6) and interleukin 8 (IL-8), The cells w ere obtained from a case of metastatic carcinoma that was originally d iagnosed to be a grade 3 (WHO classification), invasive transitional c ell carcinoma of the bladder, On microscopic observation, the cultured cells exhibited an epithelial appearance with vacuole formation in th eir cytoplasm. Ultrastructural observations revealed relatively marked microvilli and a tight junction. Significant amounts of beta-hCG, G-C SF, GM-CSF, IL-1 alpha, IL-6 and IL-8 concentrations in the supernatan t from cultured cells were demonstrated by enzyme-linked immunosorbent assays, while the expression of mRNA of these marker proteins in canc er cells was also significantly exhibited by reverse transcription pol ymerase chain reaction (RT-PCR). In addition, the expression of G-CSF receptor and IL-6 receptor mRNA was also shown by RT-PCR. Xenograft tr ansplantability using nude mice was observed in association with the p resence of severe neutrophilia in the peripheral blood, These results indicate that this cell line appears to be an effective model for the study of transitional cell carcinoma of the bladder with multipotent d ifferentiation potentials.