Hashimoto Shigenari, Takeoka Michiko, Taniguchi Shun'ichiro
Department of Molecular Oncology, Division of Molecular and Cellular Biology, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
Int J Cancer. 2003 Nov 20;107(4):557-63. doi: 10.1002/ijc.11454.
In a previous study, we demonstrated that calponin h1 suppressed tumor growth of transformed cells and that the peritonitis carcinomatosa induced by mouse B16-F10 melanoma (F10) cells was more extensive in calponin h1-deficient (CN(-/-)) mice with fragility of mesothelial (MS) cells than in their calponin h1-wild (CN(+/+)) counterparts. In our study, we assessed the therapeutic effect of calponin h1 on peritoneal dissemination. F10 cells were overlaid on the cultured CN(+/+) or CN(-/-) MS cells and the effect of calponin h1 on retraction of MS cells was evaluated. Then, an adenoviral vector with the calponin h1 gene (AdGFP-CN) inserted was constructed and was applied to CN(-/-) MS cells or CN(-/-) mouse peritoneum to investigate its suppressive effect on the peritoneal dissemination caused by F10 cells. Greater retraction and invasion of F10 cells were observed in CN(-/-) MS than in CN(+/+) cells in vitro, while down-regulation of calponin h1 was observed in CN(+/+) MS cells prior to the invasion of F10 cells. Infecting CN(-/-) MS cells with AdGFP-CN prevented their retraction and the invasion of F10 cells. Peritoneal dissemination was prominently suppressed in AdGFP-CN-infected CN(-/-) mice, and the survival of those mice was significantly prolonged. Thus, calponin h1 functioned to protect host MS cells from the invasion of F10 cells.
在先前的一项研究中，我们证明了钙调蛋白h1可抑制转化细胞的肿瘤生长，并且由小鼠B16-F10黑色素瘤（F10）细胞诱导的癌性腹膜炎在间皮（MS）细胞脆弱的钙调蛋白h1缺陷（CN(-/-)）小鼠中比在其钙调蛋白h1野生型（CN(+/+)）对应小鼠中更广泛。在我们的研究中，我们评估了钙调蛋白h1对腹膜播散的治疗效果。将F10细胞覆盖在培养的CN(+/+)或CN(-/-) MS细胞上，并评估钙调蛋白h1对MS细胞回缩的影响。然后，构建了插入有钙调蛋白h1基因的腺病毒载体（AdGFP-CN），并将其应用于CN(-/-) MS细胞或CN(-/-)小鼠腹膜，以研究其对F10细胞引起的腹膜播散的抑制作用。在体外观察到，CN(-/-) MS细胞中F10细胞回缩和侵袭比CN(+/+)细胞更明显，而在F10细胞侵袭之前，CN(+/+) MS细胞中钙调蛋白h1表达下调。用AdGFP-CN感染CN(-/-) MS细胞可阻止其回缩和F10细胞的侵袭。在AdGFP-CN感染的CN(-/-)小鼠中，腹膜播散得到显著抑制，这些小鼠的生存期显著延长。因此，钙调蛋白h1起到保护宿主MS细胞免受F10细胞侵袭的作用。
