Suppression of cancer phenotypes through a multifunctional actin‐binding protein, calponin, that attacks cancer cells and simultaneously protects the host from invasion
Suppression of cancer phenotypes through a multifunctional actin‐binding protein, calponin, that attacks cancer cells and simultaneously protects the host from invasion
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DOI：
10.1111/j.1349-7006.2005.00118.x
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发表时间：
2005-11
期刊：
影响因子：
5.7
通讯作者：
S. Taniguchi
中科院分区：
文献类型：
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作者：
S. Taniguchi
参与细胞动态功能调节的肌动蛋白细胞骨架分子的定量和/或定性改变应该与癌症表型密切相关。基于我们小组和其他人的几条实验证据，本报告提出了一种用一个分子同时攻击癌细胞并保护宿主免受癌症侵袭的策略。钙调蛋白 h1 是一种肌动蛋白稳定蛋白，也与信号转导密切相关，在人类恶性肿瘤的血管平滑肌细胞和共存的癌细胞的间皮细胞中经常受到抑制。我们培育了缺乏钙调蛋白 h1 的小鼠，其血管和腹膜表现出脆弱性。钙调蛋白h1缺陷小鼠比野生型小鼠更容易发生血行癌症转移，并且腹膜播散极其增强。通过将钙调蛋白 h1 基因外源引入腹膜间皮细胞，挽救了脆弱性。此外，将钙调蛋白 h1 基因转移到几种转化细胞系中可抑制恶性肿瘤。腹腔注射的 B16-F10 细胞的腹膜播散受到钙调蛋白 h1 基因的抑制，该基因用于靶向癌细胞和宿主的间皮细胞。该分子的多功能性质，作为细胞骨架的机械参与者和信号转导的介质，可能对癌细胞和正常细胞产生良好的受体区分作用。因此，我们相信，如果我们使用足够的多功能分子进行治疗，就有可能同时抑制癌症表型并保护正常细胞免受癌细胞的攻击。 （癌症科学 2005 年；96：738 –746）
Quantitative and/or qualitative alteration of actin cytoskeletal molecules, involved in the regulation of cellular dynamic functions, should be intimately related with cancer phenotypes. Based on several lines of experimental evidence from our group, and others, this report proposes a strategy to simultaneously attack cancer cells and protect the host from cancer invasion, with one molecule. Calponin h1, an actin‐stabilizing protein that is also intimately related to signal transduction, is very often suppressed in vascular smooth muscle cells of malignant human tumors and in mesothelial cells by coexisting cancer cells. We generated mice deficient for calponin h1, exhibiting fragility in blood vessels and peritoneal membranes. Hematogenous cancer metastasis occurred more easily in the calponin h1‐deficient mice than in wild‐type mice, and the peritoneal dissemination was extremely enhanced. The fragility was rescued by the exogenous introduction of the calponin h1 gene into mesothelial cells of the peritoneum. Furthermore, calponin h1 gene transfer into several transformed cell lines resulted in a suppression of malignancy. The peritoneal dissemination of intraperitoneally‐injected B16‐F10 cells was suppressed by the calponin h1 gene, given to target both cancer cells and the mesothelial cells of the host. The multifunctional nature of the molecule, as a machinery player of cytoskeleton and mediator of signal transduction, probably resulted in a favorable recipient‐discriminating effect on cancerous and normal cells. Thus, we believe that if we use adequate multifunctional molecules for therapy, it is possible to simultaneously suppress cancer phenotypes and protect normal cells from the attack of cancer cells. (Cancer Sci 2005; 96: 738 –746)