Tumor Cell Invasion or Metastasis Related to Calcium Sensitivity of Intracellular Locomotive Apparatus in Bladder Cancer

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Tumor Cell Invasion or Metastasis Related to Calcium Sensitivity of IntracellularLocmotive Apparatus in Bladder CancerAt first, using mouse bladder tumor cells (MBT-2 cells), the present study evaluated the functional characteristics of the actomyosin system in bladder cancer cells. The results suggest that MBT-2 cells possess a locomotive apparatus consisting of actin and myosin, and that Ca^<2+> can activate this actomyosin system, leading to the contraction or active locomotory movement of tumor cells. When cancer cells actually begin to move in the in vivo situation, it is assumed that the cells need some biological substances which can elevate the cytoplasmic Ca^<2+> level.As a candidate of such biological substances, we studied the effect of bradykinin (BK). BK was demonstrated to induce the transient rise of cytoplasmic concentration of Ca^<2+> in MBT-2 cells. Simultaneously with the increase in Ca^<2+> level, MBT-2 cells showed contraction. BK-induced Ca^<2+> transients were blocked by B2 inhibitor, but not by B_1 inhibitor, suggesting that this action of BK is mediated by B_2 subtypes.When MBT-2 cells were incubated with BK, the number of cells migrated through matrigel-coated filter was significantly greater than the control without BK.Thus, BK was also shown to induce chemoinvasion.RT-PCR clearly showed B_1 and B_2 receptor mRNAs were expressed in human bladder cancer and mouse bladder cancer. The amounts of B_2 mRNAs were 10 times greater than that of B_1 mRNAs. In addition, mRNAs of plasminogen activator, which cause a BK generation, were detected in human bladder cancer.Thus, the results from this study suggest that BK may induce locomotory movement of bladder cancer cells by mobilizing Ca^<2+> and activating actomyosin system (locomotory apparatus), which result in tumor cell invasion and metastasis.