There are no good molecular markers for prognostication or targeted therapy in bladder cancer. Most marker studies have focused on carcinoma cells, overlooking stroma. Stromal cells are known to cooperate with tumor cells to prepare invasion, but their roles are poorly understood. We reported that stellate cells (vitamin A storing cells) are often absent in bladder stroma in cancer patients. Stellate cells produce retinoic acid which is important for epithelial cell differentiation. Retinoic acid has anti-cancer effect. We propose that bladder cancer may be treated by topical use of retinoic acid, which has never been investigated.
AIMS 1) Determine the distribution of stellate cells in bladder cancer stroma, and correlate with patient outcome. 2) Determine the distribution of retinoic acid receptors in urothelial carcinoma cells, and correlate with patient outcome. 3) Determine the distribution of stellate cells and retinoic acid receptors in rat bladder cancer. 4) Identify the maximum tolerable concentration of retinoic acid in bladder instillations for rat.
HYPOTHESES 1) Low numbers of stellate cells in bladder cancer stroma predict bad patient outcome i.e. tumor recurrence, tumor progress and early death. 2) Low presence of retinoic acid receptors in urothelial carcinoma cells predicts bad outcome. 3) Some bladders in rat lack stellate cells but contain retinoic acid receptors. 4) Rats tolerate retinoic acid intravesically.