Role of galectin-3 in adenocarcinoma liver metastasis.
Galectin-3 is a lactosamine-specific lectin that binds to laminin sugar-sites, and up-regulated expression of galectin-3 in primary colorectal cancer is involved in cancer progression and metastasis. Inhibitory effects of cell adhesion and liver metastasis of adenocarcinoma via portal vein by lectin-binding sugar and anti-galectin-3 antibody was examined to determine the role of galectin-laminin binding in cancer liver metastasis. Highly metastatic adenocarcinoma cell lines XK4-A3 and RPMI4788 were used in in vitro cell attachment and nude mice liver metastatic experiments, and inhibitory effects of anti-galectin-3 antibody or lectin-binding sugars were examined. The in vitro adhesion assay demonstrated that the anti-galectin-3 antibody and alpha-lactose inhibited XK4-A3 and RPMI4788 cell adhesion to laminin in a dose-dependent manner. The liver metastasis of XK4-A3 and RPMI4788 was reduced 50 and 60%, respectively (P<0.001) by alpha-lactose treatment. Anti-galectin-3 antibody also inhibited liver metastasis in a dose-dependent manner, and maximum inhibition rate was 66% for XK4-A3 and 90% for RPMI4788. Galectin-3 plays an important role in liver metastasis of adenocarcinoma by the mechanisms of galectin-3 binding to laminin. Inhibition of galectin-3 on cancer cell surface induces reduced cell attachment to laminin and liver metastasis.
Inufusa
H
H
The First Department of Surgery, Kinki University School of Medicine, Osaka 589-8511, Japan. inufusa@surg1.med.kindai.ac.jp
Nakamura
M
M
Adachi
T
T
Aga
M
M
Kurimoto
M
M
Nakatani
Y
Y
Wakano
T
T
Miyake
M
M
Okuno
K
K
Shiozaki
H
H
Yasutomi
M
M
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D002448:Cell Adhesion / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D037502:Galectin 3; D006801:Humans; D007797:Laminin / Q000378:metabolism; D037102:Lectins / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D037502:Galectin 3; D007797:Laminin; D037102:Lectins