Oncogenic transformation and growth factor production of a human urothelial cell line

The objective of this study was to demonstrate that a nontumorigenic simian virus 40 (SV40) immortalized human urothelial cell line can be tumorigenically transformed following growth in a serum free, growth factor free, chemically defined culture system. The tumorigenicity of the cells was determined by the generation of tumors after inoculation into athymic nude mice. A cell line was derived from one of the tumors and the origin of the transformed cells was confirmed by immunohistochemical staining and analysis of the DNA fingerprint profile. Conditioned medium derived from the nontumorigenic parent cell line and the tumor line contained an activity that synergized with recombinant granulocytemacrophage colony stimulating factor (rmu GM-CSF) and recombinant macrophage colony stimulating factor (rhu M-CSF) to produce large colonies in bone marrow cultures (HPP-CFC). The concentration of human stem cell factor (SCF) and human Interleukin-I a-like activity produced by the urothelial cells was lower in the medium conditioned by the transformed tumorigenic cells than by the nontumorigenic parental cells. This data suggest that there are differences in the growth factor production of normal urothelial and tumor cells. It is possible that tumors deprived of normal levels of growth factors and nutrients may undergo further tumor progression, thus contributing to the heterogeneity seen in the clinic.