Metastasis of human colon cancer is altered by modifying expression of the beta-galactoside-binding protein galectin 3.
OBJECTIVE
Galectin 3 is a beta-galactoside-binding protein whose expression has been correlated with advanced tumor stage in the colon, but direct evidence for a role in metastasis is lacking. The current study was designed to more directly establish the role of galectin 3 in colon cancer metastasis.


METHODS
Galectin 3 levels were manipulated in human colon cancer cells using eukaryotic expression constructs designed to express the complete galectin 3 complementary DNA in either the sense or antisense orientation. Liver colonization was assessed in athymic mice after splenic-portal inoculation or after spontaneous metastasis during cecal growth.


RESULTS
Introduction of galectin 3 antisense into metastatic colon cancer cells (LSLiM6, HM7) resulted in a significant reduction in galectin 3-specific messenger RNA and total and cell surface galectin 3 protein. Conversely, stable integration of galectin 3 in the sense orientation resulted in an increase in cellular and cell surface galectin 3 in cells of low metastatic potential (LS174T). Reduction in galectin 3 levels was associated with a marked decrease in liver colonization and spontaneous metastasis by LSLiM6 and HM7 cells, whereas up-regulation of galectin 3 resulted in increased metastasis by LS174T cells.


CONCLUSIONS
This study provides direct evidence that galectin 3 plays an important role in colon cancer metastasis.
Department of Medicine, Henry Ford Health Sciences Center, Detroit, Michigan, USA.
R S
RS
Bresalier
N
N
Mazurek
L R
LR
Sternberg
J C
JC
Byrd
C K
CK
Yunker
P
P
Nangia-Makker
A
A
Raz
D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary*; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D016375:Antisense Elements (Genetics) / Q000235:genetics; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005697:Galactosides / Q000378:metabolism*; D037502:Galectin 3; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D014018:Tissue Distribution; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured
D000943:Antigens, Differentiation; D016375:Antisense Elements (Genetics); D005697:Galactosides; D037502:Galectin 3; C007816:beta-galactoside