The Key laboratory of tumor metastasis in Liaoning Province, Dalian Medical University, 9 West, Lvshun Southern Road, Dalian 116044, China.
The Key laboratory of tumor metastasis in Liaoning Province, Dalian Medical University, 9 West, Lvshun Southern Road, Dalian 116044, China.
Biomed Pharmacother. 2014 Apr;68(3):377-84. doi: 10.1016/j.biopha.2013.10.011. Epub 2013 Dec 2.
Lymph node metastasis is recognized as an important mode of liver cancer metastasis. Our previous study has built two hepatocarcinoma cell lines, Hca-F with high (75%) and Hca-P with low (25%) incidences of lymph node metastasis, and has indicated that annexin A7 is an important factor in the lymphatic metastasis of tumors. There is evidence that galectin-3 is the binding protein of annexin A7 and works in protein complexes. Our current study shows that both annexin A7 and galectin-3 express higher in Hca-F than Hca-P. Annexin A7 was successfully down-regulated in Hca-P by RNA interference, and this resulted in concomitant reduction of galactin 3 expression in annexin A7 down regulated compared to the control and N-control cells. Using CCK-8 assay, the expression level of annexin A7 and galectin-3 were found to have correlation with the proliferation ability; Transwell assay showed annexin A7 and galectin-3 are involved in cell migration and invasion regulation in mouse hepatocellular carcinoma cell lines, immunofluorescence assay indicate annexin A7 and galectin-3 were co-located annexin A7 and galectin-3 played roles in DNA damage and cell proliferation cycle checkpoint arrest pathway. Those phenomena indicated that annexin A7 influences lymphatic metastasis of tumors by interacting with galectin-3 through the regulation of tumor cell proliferation, attachment, migration and invasion.
淋巴结转移被认为是肝癌转移的重要方式。我们之前的研究构建了两个肝癌细胞系,Hca-F 具有高(75%)和 Hca-P 具有低(25%)的淋巴结转移发生率,并表明膜联蛋白 A7 是肿瘤淋巴转移的重要因素。有证据表明半乳糖凝集素-3 是膜联蛋白 A7 的结合蛋白,并在蛋白质复合物中发挥作用。我们目前的研究表明,膜联蛋白 A7 和半乳糖凝集素-3 在 Hca-F 中的表达均高于 Hca-P。通过 RNA 干扰成功下调 Hca-P 中的膜联蛋白 A7,导致与对照和 N 对照细胞相比,下调的膜联蛋白 A7 中半乳糖凝集素 3 的表达同时降低。通过 CCK-8 测定,发现膜联蛋白 A7 和半乳糖凝集素-3 的表达水平与增殖能力相关;Transwell 测定表明膜联蛋白 A7 和半乳糖凝集素-3 参与了小鼠肝癌细胞系的细胞迁移和侵袭调节,免疫荧光测定表明膜联蛋白 A7 和半乳糖凝集素-3 共定位,膜联蛋白 A7 和半乳糖凝集素-3 在 DNA 损伤和细胞增殖周期检查点阻滞途径中发挥作用。这些现象表明,膜联蛋白 A7 通过与半乳糖凝集素-3 相互作用,调节肿瘤细胞的增殖、黏附、迁移和侵袭,影响肿瘤的淋巴转移。