Novel roles of liver sinusoidal endothelial cell lectin in colon carcinoma cell adhesion, migration and in-vivo metastasis to the liver.
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.


METHODS
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.


CONCLUSIONS
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.
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China.
Yunfei
Y
Zuo
Shuangyi
S
Ren
Min
M
Wang
Biao
B
Liu
Juntao
J
Yang
Xuezhang
X
Kuai
Changwei
C
Lin
Dianyuan
D
Zhao
Li
L
Tang
Fuchu
F
He
D000328:Adult; D000368:Aged; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D003110:Colonic Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D037181:Lectins, C-Type / Q000097:blood / Q000172:deficiency / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood / Q000378:metabolism / Q000502:physiology; D009368:Neoplasm Transplantation; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D011991:Receptors, Virus / Q000172:deficiency / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D014183:Transplantation, Heterologous
C505228:CLEC4G protein, human; C561095:LSECtin protein, mouse; D037181:Lectins, C-Type; D009363:Neoplasm Proteins; D011991:Receptors, Virus; D011994:Recombinant Proteins; D019859:Proto-Oncogene Proteins c-met