IN-VITRO MODULATION OF IMPLANTATION AND INTRAEPITHELIAL EXPANSION OF BLADDER-TUMOR CELLS BY EPIDERMAL GROWTH-FACTOR

A major problem in the management of bladder cancer is the high risk f or recurrence of bladder tumors after transurethral resection. This ha s generally been attributed to the attachment and subsequent expansion of exfoliated tumor cells to the traumatized bladder wall. An in vitr o cocultivation model was used to study the implantation and growth of human tumor cells in traumatized murine urothelium. Furthermore, we i nvestigated in a time-course experiment whether stimulation of the reg enerative activity of the normal urothelium by a growth factor could a ffect implantation and subsequent growth of bladder tumor cells. After inoculation on injured confluent cultures of murine urothelium, human T24 and SD bladder carcinoma cells preferentially attached to the den uded areas. SD cells expanded into the normal urothelium as a sharply demarcated tumor, while T24 cells infiltrated as single cells. Treatme nt of the primary urothelium with epidermal growth factor (EGF) stimul ated the proliferation of the primary urothelium and reduced the impla ntation and growth of T24 considerably. EGF reduced the implantation o f the SD tumor cells but could not prevent the further expansion at th e expense of surrounding normal urothelium. Since EGF had no effect on migration or proliferation of SD or T24 cells, its modulation of expa nsive growth is most probably due to an increase in the regeneration o f normal urothelium. This study suggests that recurrence of transition al cell carcinomas might in some instances be inhibited by stimulation of the regeneration of traumatized urothelium. The reported in vitro cocultivation model may be useful for studying additional factors invo lved in intraepithelial expansion of carcinoma cells. (C) 1997 Academi c Press.