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

膀胱癌肿瘤细胞侵袭或转移与细胞内运动装置钙敏感性相关

• 批准号: 07671743
• 负责人: YAMAGUCHI Osamu
• 金额: $ 1.6万
• 依托单位: Fukushima Medical University, School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671743/
• 关键词: bladder tumor; bradykinin; calcium ion; contractile protein; cell metility; invasion; metastasis; ブラディキニン受容体

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.

膀胱癌细胞内运动装置钙敏感性相关的肿瘤细胞侵袭或转移本研究首先利用小鼠膀胱肿瘤细胞（MBT-2细胞）评估了膀胱癌细胞中肌动球蛋白系统的功能特征。结果提示MBT-2细胞具有由肌动蛋白和肌球蛋白组成的运动装置，Ca 2+ 可以激活该肌动球蛋白系统，导致肿瘤细胞收缩或主动运动。当癌细胞在体内实际开始移动时，假设细胞需要一些可以提高细胞质Ca^2+水平的生物物质。作为此类生物物质的候选者，我们研究了缓激肽的作用（BK）。证明BK诱导MBT-2细胞中Ca 2+ 细胞质浓度的瞬时升高。随着Ca 2+ 水平的增加，MBT-2细胞显示收缩。 BK 诱导的 Ca^2+ 瞬变被 B2 抑制剂阻断，但不被 B_1 抑制剂阻断，表明 BK 的这种作用是由 B_2 亚型介导的。当 MBT-2 细胞与 BK 一起孵育时，迁移通过的细胞数量基质胶包被的滤膜显着大于没有 BK 的对照。因此，BK 也显示出诱导化学侵袭。RT-PCR 清楚地显示 B_1 和 B_2 受体 mRNA 表达在人类膀胱癌和小鼠膀胱癌中。 B_2 mRNA的量是B_1 mRNA的10倍。此外，在人膀胱癌中检测到导致BK生成的纤溶酶原激活剂的mRNA。因此，本研究的结果表明BK可能通过动员Ca^2+和激活肌动球蛋白来诱导膀胱癌细胞的运动系统（运动装置），导致肿瘤细胞侵袭和转移。