C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma
C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma
复制标题
DOI：
10.1007/s00535-013-0773-6
复制
发表时间：
2014-01-01
影响因子：
6.3
通讯作者：
Todo, Satoru
中科院分区：
文献类型：
--
作者：
Kawamata, Futoshi;Homma, Shigenori;Todo, Satoru
背景淋巴结转移是结直肠癌(CRC)进展的关键事件。间充质蛋白在多种类型的恶性肿瘤中均有表达，且与不良预后有关。全长的间硫蛋白(Full-ERC)被酶切成膜结合的C-ERC/Mesothelin和N-ERC/Mesothelin，分泌到血液中。本研究的目的是通过临床病理分析和体外淋巴侵袭试验，探讨间皮蛋白在结直肠癌中的生物学作用。方法对91例结直肠癌标本进行免疫组织化学检测，并对其在管腔膜和/或胞浆中的定位进行评价。结果免疫组织化学结果显示，37.4%的人结直肠癌细胞系中的间皮蛋白表达与淋巴渗透和淋巴结转移有关，而与患者的预后无关。有趣的是，在有淋巴结转移的患者(N=38)中，间硫蛋白的“腔膜阳性”与不良患者的预后显著相关。此外，淋巴侵袭实验显示Full-WiDR和C-WiDR对人淋巴管内皮细胞的侵袭作用明显高于Mock-WiDR(P<；0.01)。结论结直肠癌淋巴结转移患者的预后不良可能与其腔膜上的Mesothelin表达有关。此外，这是首次在体外证明C-ERC/Mesothelin与肿瘤淋巴侵袭相关的生物学功能。
Background Lymph node metastasis is a key event of colorectal cancer (CRC) progression. Mesothelin is expressed in various types of malignant tumor and associated with an unfavorable prognosis. The full-length mesothelin (Full-ERC) is cleaved by protease into membrane-bound C-ERC/mesothelin and N-ERC/mesothelin which is secreted into the blood. The aim of this study was to examine the biological role of mesothelin in CRC by clinicopathological analysis and in vitro lymphatic invasion assay.Methods Ninety-one cases of CRC specimens were immunohistochemically examined and the localization of mesothelin in luminal membrane and/or cytoplasm was also evaluated. Lymphatic invasion assay was also performed using the human CRC cell line, WiDr, which was transfected with Full-, N- and C-ERC/mesothelin expression plasmids (Full-WiDr, N-WiDr and C-WiDr).Results Immunohistochemically, "luminal membrane positive" of mesothelin was identified in 37.4 %, and correlated with lymphatic permeation and lymph node metastasis, but not with patients' prognosis. Interestingly, among the patients with lymph node metastasis (N = 38), "luminal membrane positive" of mesothelin significantly correlated with unfavorable patients' outcome. In addition, lymphatic invasion assay revealed that Full-WiDr and C-WiDr more significantly invaded human lymphatic endothelial cells than the Mock-WiDr (P < 0.01).Conclusion The luminal membrane expression of mesothelin was associated with unfavorable prognosis of CRC patients with lymph nodemetastasis. Moreover, this is the first report to prove the biological function of C-ERC/mesothelin associated with lymphatic invasion of cancer in vitro.