MP21-17 EFFECTS OF ADIPOSE TISSUE STROMAL CELLS ON APOPTOSIS, GROWTH AND INVASION OF SUPERFICIAL AND INVASIVE TYPE UROTHELIAL CARCINOMAS OF THE BLADDER

Abstract

INTRODUCTION AND OBJECTIVES: Cancer-stromal interaction is critical for cancer biology. Bladder cancer develops within the mucosa, and invades into muscle layer surrounded by abundant adipose tissue. Adipose tissue has stromal cell types, such as preadipocytes and mesenchymal stem cells (MSCs). Thus, the adipose tissue stromal cells (ATSCs) seem critical for bladder cancer biology. The aim of this study is to address the effects of ATSCs on the apoptosis, growth and invasion of the superficial and invasive types. METHODS: RT4 and RT112 were used as human superficial urothelial carcinoma type of bladder, while EJ and HT1376 were done as invasive type. ATSCs were isolated from subcutaneous adipose tissue of 1-week old male Wister rats. We examined the apoptosis, growth and invasion of cancer cells, using collagen gel invasion assay system, in which the tumor cells were co-cultured on ATSC-embedded gel layer. The cellular behavior, and the apoptosis-, growthand ivasion-related molecules were analyzed by morphometry, immunohistochemistry, Western blot and real-time RT-PCR. RESULTS: ATSCs promoted and inhibited the apoptosis and growth of superficial type cancer cells, respectively. In contrast, ATSCs inhibited and promoted the apoptosis and growth of invasive type cancer cells. ATSCs had no effect on the invasion of superficial type, whereas they promoted the invasion of invasive type. ATSCs promoted the expression of MAPK proteins (raf-1, MEK-1 and ERK1/ERK2) in all cancer cell types. In turn, superficial type promoted [alpha]-SMA-positive myofibroblastic differentiation in ATSCs, while invasive type did lipid dropletand S-100 protein-positive adipogenic differentiation in ATSCs. CONCLUSIONS: The data suggest the following issues: 1) ATSCs suppress the progression of superficial type urothelial carcinoma through the growth inhibition and apoptosis promotion, whereas ATSCs promote that of invasive type through the enhancement of the growth and invasion, and the apoptosis prohibition; 2) ATSCinduced MAPK pathway activation plays differential roles in biological behavior of superficial and invasive types; and 3) Superficial type induces myofibroblastic differentiation in ATSCs as cancer-associated phenotype, while invasive type does adipogenic differentiation in ATSCs. Source of Funding: none