Novel roles of DC-SIGNR in colon cancer cell adhesion, migration, invasion, and liver metastasis.
Novel roles of DC-SIGNR in colon cancer cell adhesion, migration, invasion, and liver metastasis.
复制标题
DC-SIGNR在结肠癌细胞粘附、迁移、侵袭和肝转移中的新作用
DOI：
10.1186/s13045-016-0383-x
复制
发表时间：
2017-01-21
影响因子：
28.5
通讯作者：
Zuo Y
中科院分区：
文献类型：
--
作者：
Na H;Liu X;Li X;Zhang X;Wang Y;Wang Z;Yuan M;Zhang Y;Ren S;Zuo Y
背景肿瘤转移是导致结肠癌预后不良的重要原因。DC-SIGNR是一种c型凝集素，常见于人肝窦内皮细胞。LSECtin是DC-SIGNR的同源物，已被证明参与结肠癌肝转移。由于两种蛋白在表达模式和结构上的相似性，我们推测DC-SIGNR也可能参与了这一过程。方法用DC-SIGNR蛋白或对照IgG处理结肠癌细胞，观察细胞迁移、侵袭及形态变化。采用异种移植小鼠模型研究DC-SIGNR在体内结肠癌肝转移中的作用。此外，我们还利用人类基因表达阵列检测DC-SIGNR蛋白刺激下结肠癌细胞的差异基因表达。采用ELISA法检测结肠癌患者血清DC-SIGNR水平，探讨DC-SIGNR的意义。结果我们研究了DC-SIGNR是否促进结肠癌细胞的粘附、迁移和侵袭。敲除小鼠DC-SIGNR可降低结肠癌细胞的肝转移能力，延长存活时间。表达人DC-SIGNR增强结肠癌肝转移。此外，DC-SIGNR通过上调各种金属硫蛋白亚型，赋予癌细胞转移能力。为了验证上述结果，我们还发现有肝转移的结肠癌患者血清DC-SIGNR水平高于无肝转移的结肠癌患者。结论DC-SIGNR可能促进结肠癌的肝转移，是一种有前景的抗癌靶点。
BackgroundTumor metastasis is an essential cause of the poor prognosis of colon cancer. DC-SIGNR is a C-type lectin that is frequently found on human liver sinusoidal endothelial cells. LSECtin, which is a homologue of DC-SIGNR, has been demonstrated to participate in colon cancer liver metastasis. Due to the similarities in the expression pattern and structure of the two proteins, we speculated that DC-SIGNR could also be involved in this process.MethodsColon cancer cells were treated with the DC-SIGNR protein or control IgG, after which cell migration, invasion, and morphology were assayed. Xenograft mouse models were used to determine the role of DC-SIGNR in colon cancer liver metastasis in vivo. In addition, a human gene expression array was used to detect differential gene expression in colon cancer cells stimulated with the DC-SIGNR protein. The serum level of DC-SIGNR was examined in colon cancer patients by ELISA, and the significance of DC-SIGNR was determined.ResultsIn our research, we investigated whether DC-SIGNR promotes colon cancer cell adhesion, migration, and invasion. Knocking down mouse DC-SIGNR decreased the liver metastatic potency of colon cancer cells and increased survival time. Expressing human DC-SIGNR enhanced colon cancer liver metastasis. Furthermore, DC-SIGNR conferred metastatic capability on cancer cells by upregulating various metallothionein isoforms. To validate the above results, we also found that the serum DC-SIGNR level was statistically higher in colon cancer patients with liver metastasis compared with those without metastasis.ConclusionsThese results imply that DC-SIGNR may promote colon carcinoma hepatic metastasis and could serve as a promising therapeutic target for anticancer treatment.