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半乳糖凝集素-3与癌胚抗原之间的协同相互作用促进结直肠癌转移。

Synergistic interaction between galectin-3 and carcinoembryonic antigen promotes colorectal cancer metastasis.

作者信息

Wu Keng-Liang, Huang Eng-Yen, Yeh Wen-Ling, Hsiao Chang-Chun, Kuo Chung-Mou

机构信息

Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.

Graduate Institute of Clinical Medical Sciences, Chang Gung University, Kaohsiung, Taiwan.

出版信息

Oncotarget. 2017 Jun 27;8(37):61935-61943. doi: 10.18632/oncotarget.18721. eCollection 2017 Sep 22.

Abstract

In this study, we investigated the role of galectin-3 and carcinoembryonic antigen (CEA) in metastasis and survival of colorectal cancer (CRC) patients. CEA interacted with galectin-3 at the cell surface and cytoplasm of Caco2 and DLD1 CRC cells. Knocking down galectin-3 did not affect CEA expression in CRC cells. However, there was a dose-dependent increase in CRC cell migration upon addition of small amounts of exogenous CEA (≤1ng/ml). Galectin-3 knockdown blocked induction of CRC cell migration by CEA, suggesting interaction between galectin-3 and CEA was necessary for CRC cell migration. Exogenous CEA and galectin-3 synergistically promoted migration of galectin-3 knockdown DLD1 cells. Immunohistochemical analysis showed that CEA co-localized with galectin-3 in CRC patient tissues. In additon, advanced stage CRC patients had higher serum galectin-3 and CEA levels than early stage CRC patients. High serum CEA and galectin-3 levels correlated with advanced N stage and poor survival in CRC patients. These findings suggest interaction between galectin-3 and CEA promotes CRC migration and metastasis, and correlates with poor survival of CRC patients. Thus combinatorial therapy targeting galectin-3 and CEA may improve outcomes for advanced stage CRC patients.

摘要

在本研究中,我们调查了半乳糖凝集素-3和癌胚抗原(CEA)在结直肠癌(CRC)患者转移和生存中的作用。CEA在Caco2和DLD1 CRC细胞的细胞表面和细胞质中与半乳糖凝集素-3相互作用。敲低半乳糖凝集素-3不影响CRC细胞中CEA的表达。然而,添加少量外源性CEA(≤1ng/ml)后,CRC细胞迁移呈剂量依赖性增加。半乳糖凝集素-3敲低可阻断CEA诱导的CRC细胞迁移,提示半乳糖凝集素-3与CEA之间的相互作用是CRC细胞迁移所必需的。外源性CEA和半乳糖凝集素-3协同促进半乳糖凝集素-3敲低的DLD1细胞迁移。免疫组织化学分析显示,在CRC患者组织中CEA与半乳糖凝集素-3共定位。此外,晚期CRC患者血清半乳糖凝集素-3和CEA水平高于早期CRC患者。高血清CEA和半乳糖凝集素-3水平与CRC患者的晚期N分期和不良生存相关。这些发现提示半乳糖凝集素-3与CEA之间的相互作用促进CRC迁移和转移,并与CRC患者的不良生存相关。因此,针对半乳糖凝集素-3和CEA的联合治疗可能改善晚期CRC患者的预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e32/5617476/722fd83c88a3/oncotarget-08-61935-g001.jpg

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