Abstract
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.
Highlights
Tumor metastasis is an essential cause of the poor prognosis of colon cancer
We found that colon cancer patients with liver metastasis showed higher levels of DC-SIGNR compared with patients without metastasis
Recombinant DC-SIGNR protein adheres to LoVo, LS174T, and HCT-116 cells Because DC-SIGNR acts as an adhesion receptor, we first wondered whether DC-SIGNR was associated with the metastatic potential of colon cancer cells
Summary
DC-SIGNR is a C-type lectin that is frequently found on human liver sinusoidal endothelial cells. LSECtin, which is a homologue of DCSIGNR, has been demonstrated to participate in colon cancer liver metastasis. Tissue-specific interactions play a critical role in the initiation of tumor metastasis This process is regulated by specific tissue. DC-SIGNR, dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin-related protein, is a C-type II integral membrane protein. It is predominantly found on the sinusoidal endothelial cells in the liver and lymph nodes as well as in the placental endothelium [7]. The mannose receptor promoted colon carcinoma cell interaction with the liver sinusoidal endothelium and contributed to colon cancer hepatic metastasis, which was induced by interleukin-1 [16]. We hypothesized that DC-SIGNR could be associated with human colon cancer progression
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