BACILLUS-CALMETTE-GUERIN ENHANCES PRODUCTION AND SECRETION OF TYPE-IVCOLLAGENASES IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS

Intravesical administration of bacillus Calmette-Guerin (BCG) is an ef fective and widely accepted treatment for superficial bladder cancer. Rapid progression of the disease after BCG therapy, however, has been reported in some cases refractory to the treatment. We examined whethe r BCG treatment and coexistence of peripheral blood mononuclear cells (PBMCs) alter the invasive potential of bladder cancer cells. Producti on and secretion of two type IV collagenases, matrix metalloproteinase (MMP) 2 and MMP 9, by PBMCs from five healthy donors or bladder cance r cells (T24, JTC 30, and JTC 32) were evaluated by gelatin zymography , western blot analysis, and northern blot analysis. Invasion of bladd er cancer cells was also examined using reconstituted basement membran e (Matrigel). BCG (5, 50, and 500 mu g/ml) had no effect on secretion of MMP 2 and MMP 9 by bladder cancer cells, but increased the producti on and secretion of MMP 9 by PBMCs in a dose-dependent manner. The coe xistence of PBMCs increased invasion of T24 cells and BCG further enha nced the invasion. Thus, BCG promotes invasion of bladder cancer cells under certain conditions. An increase in the secretion of MMP 9 by PB MCs may account in part for the effect.