Galectin-9 as a prognostic factor with antimetastatic potential in breast cancer.
OBJECTIVE
Galectin-9, a member of the beta-galactoside-binding galectin family, induces aggregation of certain cell types. We assessed the contribution of galectin-9 to the aggregation of breast cancer cells as well as the relation between galectin-9 expression in tumor tissue and distant metastasis in patients with breast cancer.


METHODS
Subclones of MCF-7 breast cancer cells with high or low levels of galectin-9 expression were established and either cultured on plastic dishes or transplanted into nude mice. The tumors of 84 patients with breast cancer were tested for galectin-9 expression by immunohistochemistry. The patients were followed up for 14 years.


RESULTS
MCF-7 subclones with a high level of galectin-9 expression formed tight clusters during proliferation in vitro, whereas a subclone (K10) with the lowest level of galectin-9 expression did not. However, K10 cells stably transfected with a galectin-9 expression vector aggregated in culture and in nude mice. Ectopic expression of galectin-9 also reduced MCF-7 cell adhesion to extracellular matrix proteins. Tumors of 42 of the 84 patients were galectin-9 positive, and those of 19 of the 21 patients with distant metastasis were galectin-9 negative. None of the 13 patients with galectin-9-positive tumors and lymph node metastasis up to level II manifested distant metastasis. The cumulative disease-free survival ratio for galectin-9-positive patients was more favorable than that for the galectin-9-negative group (P < 0.0001). Multivariate analysis revealed that galectin-9 status influenced distant metastasis independently of and to a greater extent than lymph node metastasis.


CONCLUSIONS
Galectin-9 is a possible prognostic factor with antimetastatic potential in breast cancer.
Irie
Akemi
A
Second Department of Surgery, School of Medicine, Kagawa University and GalPharma Co. Ltd., Kagawa, Japan.
Yamauchi
Akira
A
Kontani
Keiichi
K
Kihara
Minoru
M
Liu
Dage
D
Shirato
Yukako
Y
Seki
Masako
M
Nishi
Nozomu
N
Nakamura
Takanori
T
Yokomise
Hiroyasu
H
Hirashima
Mitsuomi
M
D000328:Adult; D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D002449:Cell Aggregation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018572:Disease-Free Survival; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D037161:Galectins / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010957:Plasmids / Q000235:genetics; D011379:Prognosis; D014162:Transfection; D014183:Transplantation, Heterologous
D016326:Extracellular Matrix Proteins; D037161:Galectins; C105032:LGALS9 protein, human