MODULATION OF INTRAEPITHELIAL EXPANSION OF HUMAN T24 BLADDER-CARCINOMA CELLS IN MURINE UROTHELIUM BY GROWTH-FACTORS AND EXTRACELLULAR-MATRIX COMPONENTS

The high recurrence rate of bladder cancer is probably due to an effic ient repopulation of the bladder by residual transformed cells after r esection of the tumour. However, the regenerating capacity of the norm al urothelial cells is very high. To study the balance between regener ating normal urothelium and outgrowth of transformed urothelial cells, we recently developed an in vitro co-cultivation model. With this mod el system we studied the effects of growth factors and extracellular-m atrix components on the intra-epithelial expansion of human T24 bladde r-carcinoma cells in primary mouse-bladder explants. Exposure of the c ultures to acidic fibroblast growth factor (aFGF) and laminin led to a dramatic increase in the number of invasive T24 cells into the primar y urothelium. Epidermal growth factor (EGF) and collagen types I and I V counteracted the infiltration of individual T24 cells. EGF, aFGF, la minin and collagen types I and IV did not directly affect the migratio n and proliferation of T24 cells. Apparently, the efficacy of invasion of transformed urothelial cells into primary urothelium is not only d ependent on the intrinsic characteristics of the transformed cells, bu t can be influenced to a considerable extent by exogenous components e xerting their influence on the normal urothelium. The clinical relevan ce of this observation needs to be studied further. (C) 1995 Wiley-Lis s, Inc.