P-cadherin promotes ovarian cancer dissemination through tumor cell aggregation and tumor-peritoneum interactions.
P-cadherin promotes ovarian cancer dissemination through tumor cell aggregation and tumor-peritoneum interactions.
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DOI：
10.1158/1541-7786.mcr-13-0489
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发表时间：
2014-04
期刊：
影响因子：
--
通讯作者：
Naora H
中科院分区：
文献类型：
--
作者：
Usui A;Ko SY;Barengo N;Naora H
More than 60% of patients who are diagnosed with epithelial ovarian cancer (EOC) present with extensive peritoneal carcinomatosis. EOC cells typically disseminate by shedding into the peritoneal fluid where they survive as multi-cellular aggregates and then implant onto peritoneal surfaces. However, the mechanism that facilitates aggregation and implantation of EOC cells is poorly understood. The cell adhesion molecule P-cadherin (CDH3) has been reported to be induced during early progression of EOC and to promote tumor cell migration. In this study, P-cadherin not only promoted migration of EOC cells, but also facilitated the assembly of floating EOC cells into multi-cellular aggregates and inhibited anoikis in vitro. Furthermore, inhibiting P-cadherin by shRNAs or a neutralizing antibody prevented EOC cells from attaching to peritoneal mesothelial cells in vitro. In mouse intraperitoneal xenograft models of EOC, inhibition of P-cadherin decreased the aggregation and survival of floating tumor cells in ascites and reduced the number of tumor implants on peritoneal surfaces. These findings indicate that P-cadherin promotes intraperitoneal dissemination of EOC by facilitating tumor cell aggregation and tumor-peritoneum interactions in addition to promoting tumor cell migration. Inhibiting P-cadherin blocks multiple, key steps of EOC progression and has therapeutic potential.
