Suppression of peritoneal dissemination through protecting mesothelial cells from retraction by cancer cells
Suppression of peritoneal dissemination through protecting mesothelial cells from retraction by cancer cells
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DOI：
10.1002/ijc.11454
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发表时间：
2003-11
影响因子：
6.4
通讯作者：
S. Hashimoto;M. Takeoka;S. Taniguchi
中科院分区：
文献类型：
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作者：
S. Hashimoto;M. Takeoka;S. Taniguchi
在先前的研究中，我们证明了钙调蛋白h1抑制转化细胞的肿瘤生长，并且在具有间皮细胞（MS）脆性的钙调蛋白h1缺陷（CN-/-）小鼠中，由小鼠B16-F10黑色素瘤（F10）细胞诱导的癌性腹膜炎比其钙调蛋白h1-野生（CN+/+）对应物更广泛。在我们的研究中，我们评估了钙调蛋白h1对腹膜播散的治疗作用。将F10细胞覆盖在培养的CN+/+或CN-/-MS细胞上，并评价钙调蛋白h1对MS细胞收缩的影响。然后，构建了插入了calponin 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CN−/− MS中观察到F10细胞比CN+/+细胞更大的收缩和侵袭，而在CN+/+ MS细胞中观察到F10细胞侵袭前calponin h1的下调。用AdGFP‐CN感染CN−/− MS细胞阻止了它们的回缩和F10细胞的侵袭。在AdGFP‐CN‐感染的CN−/−小鼠中，腹膜播散受到显著抑制，这些小鼠的存活时间显著延长。因此，钙调蛋白h1的作用是保护宿主MS细胞免受F10细胞的侵袭。© 2003 Wiley利斯公司
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. © 2003 Wiley‐Liss, Inc.