Role of sialyl Lewis X in liver metastasis in view of liver-associated immunity.
OBJECTIVE
As sialyl Lewis X is a lignad of the selectin family, it has been proposed that sialyl Lewis X-rich colon cancer cells metastasize to the liver by adhesion to selectins on hepatic endothelial cells. However, little is known about the interaction between sialyl Lewis X and hepatic immune cells. We evaluated the role of sialyl Lewis X in liver metastasis in view of liver-associated immunity.


METHODS
RCN-9, a colonic cancer cell line derived from Fischer rats, and its subclone RCN-H4, which exhibited high metastatic potential to the liver, were used. In an attempt to investigate the underlying basis for the difference in hepatic metastasis formation, we assessed the susceptibility of both cell lines to lysis by hepatic sinusoidal lymphocytes in 51Cr-release assays, and the expression of a number of carbohydrate antigens by both cell lines by flow cytometry.


RESULTS
Hepatic sinusoidal lymphocytes mainly consist of natural cytotoxic lymphocytes, including NKT cells. The H4 colonic cancer subclone showed decreased susceptibility to lysis by hepatic sinusoidal lymphocytes, as compared to the parent cell line. In addition, a significant increase of sialyl Lewis X expression was noted in the H4 subclone. Neuraminidase treatment of H4 cells increased their susceptibility to hepatic sinusoidal lymphocyte-mediated killing. Furthermore, rats inoculated with neuraminidase-treated H4 cells produced fewer metastatic nodules in the liver than those inoculated with untreated H4 cells.


CONCLUSIONS
Sialyl Lewis X expression in tumor cells reduced their susceptibility to hepatic sinusoidal lymphocyte-mediated killing, and thus, may facilitate the ability of the tumor cells to metastasize to the liver.
Okuno
Kiyotaka
K
First Department of Surgery, Kinki University School of Medicine, 377-2 Ohno-higashi, Osaka-sayama 589-8511, Japan. okuno@surg1.med.kindai.ac.jp
Kawai
Isao
I
Hirai
Norihiko
N
Narimatsu
Hisashi
H
Yasutomi
Masayuki
M
D000230:Adenocarcinoma / Q000276:immunology* / Q000556:secondary*; D000818:Animals; D003110:Colonic Neoplasms / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008114:Liver Neoplasms, Experimental / Q000276:immunology* / Q000556:secondary*; D009439:Neuraminidase / Q000494:pharmacology; D009844:Oligosaccharides / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D000080506:Sialyl Lewis X Antigen; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology*; D019139:Tumor Escape / Q000187:drug effects / Q000276:immunology
D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D009439:Neuraminidase