Objective Adhesion molecules play an important role in tumour metastasis. The liver is a frequent target for the metastasis of several tumour types. However, virtually no liver-specific adhesion molecules have been described in terms of organ-specific metastasis. This study aimed to determine the role of liver sinusoidal endothelial cell lectin (LSECtin) in colon carcinoma metastasis to the liver.
Design The role of LSECtin in colon carcinoma metastasis to the liver was determined by LSECtin knockout nude mice and anti-LSECtin antibody. LSECtin promoting the migration of LS174T and LoVo cells was determined by transwell experiment. The serum levels of soluble LSECtin in patients were elevated by ELISA.
Results LSECtin was found to adhere to LS174T and LoVo colon cancer cells in vitro and in vivo. Deficiency or blocking of LSECtin significantly decreased hepatic metastases of LS174T and LoVo cells. Primary colon cancer cells from patients also exhibited remarkably low rates of hepatic metastasis in LSECtin knockout mice. LSECtin promoted the migration of LS174T and LoVo cells and increased the expression of c-Met in these cells. Serum soluble LSECtin was detected at significantly higher levels in colon cancer patients with or without hepatic metastases compared with healthy controls and was also increased in colon cancer patients with metastases compared with those without metastases.
Conclusion The results indicate that LSECtin plays an important role in colorectal carcinoma liver metastasis and may be a promising new target for intervention in metastasis formation.
- Abdominal surgery
- adhesion molecule
- cell adhesion
- colorectal carcinoma
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LT and FH contributed equally and share last authorship.
Funding This study was supported by grants from Chinese National Natural Science Foundation Projects (30872288 and 30870550), the Chinese State Key Program in Basic Research (2009CB521804, 2010CB911900 and 2012AA020206-2).
Competing interests None.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.