Wu Keng-Liang, Huang Eng-Yen, Yeh Wen-Ling, Hsiao Chang-Chun, Kuo Chung-Mou
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.
Oncotarget. 2017 Jun 27;8(37):61935-61943. doi: 10.18632/oncotarget.18721. eCollection 2017 Sep 22.
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.
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。