Novel roles of DC-SIGNR in colon cancer cell adhesion, migration, invasion, and liver metastasis.
BACKGROUND
Tumor 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.


METHODS
Colon 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.


RESULTS
In 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.


CONCLUSIONS
These results imply that DC-SIGNR may promote colon carcinoma hepatic metastasis and could serve as a promising therapeutic target for anticancer treatment.
['Na|Heya|H|', 'Liu|Xiaoli|X|', 'Li|Xiaomeng|X|', 'Zhang|Xinsheng|X|', 'Wang|Yu|Y|', 'Wang|Zhaohui|Z|', 'Yuan|Menglang|M|', 'Zhang|Yu|Y|', 'Ren|Shuangyi|S|', 'Zuo|Yunfei|Y|']
D000818:Animals D002448:Cell Adhesion D015815:Cell Adhesion Molecules D002465:Cell Movement D003110:Colonic Neoplasms D004195:Disease Models, Animal D064593:Heterografts D006801:Humans D037181:Lectins, C-Type D008113:Liver Neoplasms D051379:Mice D009361:Neoplasm Invasiveness D009362:Neoplasm Metastasis D011956:Receptors, Cell Surface D014407:Tumor Cells, Cultured
DC-SIGNR Colon cancer liver metastasis Metallothioneins