贺福初院士组癌转移新发现登国际著名刊物

　　

   军事医学科学院放射与辐射医学研究所、北京蛋白质组研究中心、蛋白质组学国家重点实验室贺福初院士、唐丽副研究员课题组，最近在国际著名的消化病杂志《Gut》上发表了题为“Novel roles of liver sinusoidal endothelial cell lectin in colon carcinoma cell adhesion, migration and in-vivo metastasis to the liver”的研究论文，解析了结肠癌肝转移的新机制并证明结肠癌的肝内转移可被特异性抗体抑制。

   一直以来，恶性肿瘤的侵袭和转移是影响病患预后和导致死亡的重要因素。在结肠癌发生转移的病例中，40～70％的结肠癌死亡患者与肝转移有关。而在恶性肿瘤的预防和治疗上“早诊断、早治疗”一直是现代医学的最高追求。因此，研究结肠癌肝转移机制，寻找肿瘤转移的早期标志物是提高结肠癌患者存活率的重要手段之一。

   贺福初院士实验室唐丽、杨俊涛、刘万里博士等前期从肝脏中发现了一种新的跨膜糖蛋白LSECtin，并证实该蛋白是一种肝脏特异表达的免疫细胞负调控分子（相关成果于2009年发表于国际顶级的消化病杂志《Gastroenterology》，2009,137(4):1498-508）。

   在此基础上，唐丽课题组博士后左云飞等科研人员通过近5年的潜心探索，发现LSECtin是一种新的结肠癌细胞粘附分子；将结肠癌细胞株或结肠癌患者来源的结肠癌细胞接种于LSECtin基因敲除裸鼠，其向肝脏转移率显著降低；受此启示，他们继而证明LSECtin抗体能明显降低结肠癌细胞株往肝脏的迁移。其进一步的机制研究表明LSECtin蛋白可以诱导结肠癌细胞株c-Met（肝细胞生长因子受体）高表达，从而促进结肠癌细胞向肝脏的迁移。研究人员还对结肠癌患者临床标本进行了检测和分析，发现结肠癌肝转移患者血清中的可溶性LSECtin(sLSECtin)表达水平明显高于正常人和未发生肝转移的结肠癌患者，提示它可能作为结肠癌肝转移的生物标志物。

   LSECtin是我国自主发现的一种新型跨膜糖蛋白。上述成果表明LSECtin抗体或小分子药物（阻断LSECtin的功能）有可能用于治疗结肠癌肝转移、sLSECtin有可能作为结肠癌肝转移早期诊断的标志物。  
该研究得到国家自然科学基金、863计划和973计划等项目的联合资助。

原文摘要：

Novel roles of liver sinusoidal endothelial cell lectin in colon carcinoma cell adhesion, migration and in-vivo metastasis to the liver
Objective Adhesion molecules play an important role in tumour metastasis. The liver is a frequent target for the metastasis of several tumour types. However, virtually no liver-specific adhesion molecules have been described in terms of organ-specific metastasis. This study aimed to determine the role of liver sinusoidal endothelial cell lectin (LSECtin) in colon carcinoma metastasis to the liver.

Design The role of LSECtin in colon carcinoma metastasis to the liver was determined by LSECtin knockout nude mice and anti-LSECtin antibody. LSECtin promoting the migration of LS174T and LoVo cells was determined by transwell experiment. The serum levels of soluble LSECtin in patients were elevated by ELISA.

Results LSECtin was found to adhere to LS174T and LoVo colon cancer cells in vitro and in vivo. Deficiency or blocking of LSECtin significantly decreased hepatic metastases of LS174T and LoVo cells. Primary colon cancer cells from patients also exhibited remarkably low rates of hepatic metastasis in LSECtin knockout mice. LSECtin promoted the migration of LS174T and LoVo cells and increased the expression of c-Met in these cells. Serum soluble LSECtin was detected at significantly higher levels in colon cancer patients with or without hepatic metastases compared with healthy controls and was also increased in colon cancer patients with metastases compared with those without metastases.

Conclusion The results indicate that LSECtin plays an important role in colorectal carcinoma liver metastasis and may be a promising new target for intervention in metastasis formation.