Upregulation of galectins-1 and -3 in human colon cancer and their role in regulating cell migration.
To probe the potential contribution of beta-galactoside-contributing epitopes and receptor proteins (gal-1 and gal-3) to colon malignancy, we first examined the expression of galectins and binding sites in clinical specimens by lectin and immunohistochemistry. Sixty-seven colonic surgical resections were studied, including 10 normal, 10 mild dysplasias, 10 severe dysplasias and 37 cancers. gal-1 and gal-3 were expressed in variable amounts in the epithelial cells and the connective tissue of normal colon. Their expression significantly increased with the degree of dysplasia, suggesting that gal-1 and gal-3 and their binding sites are related to malignant progression, while gal-8 has been associated with suppressor activity. To study the functional aspects, the influence of these galectins on the migration of 4 human colorectal cancer cell lines (HCT-15, LoVo, DLD-1, CoLo201) was studied. In agreement with histopathologic monitoring, these tumor cells were found to produce gal-3, while only CoLo201 was positive for gal-1. Except for DLD-1 and gal-1, the lines exhibited gal-1 binding sites on the surface, prompting study by computer-assisted videomicroscopy of the effect on cell migration of the presence of galectin on the culture substrate. The level of cell migration for HCT-15, LoVo and CoLo201 cells was significantly reduced by 0.15 microg/cm(2) gal-1, and the presence of a blocking antibody at least reduced this effect. gal-3 significantly reduced cell migration in all 4 of the in vitro cell lines.
Hittelet
Axel
A
Laboratory of Gastroenterology, Erasmus Hospital, Brussels, Belgium.
Legendre
Hugues
H
Nagy
Nathalie
N
Bronckart
Yves
Y
Pector
Jean-Claude
JC
Salmon
Isabelle
I
Yeaton
Paul
P
Gabius
Hans-Joachim
HJ
Kiss
Robert
R
Camby
Isabelle
I
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002465:Cell Movement; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D017931:DNA Primers / Q000737:chemistry; D037483:Galectin 1 / Q000235:genetics / Q000378:metabolism*; D037501:Galectin 2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D037102:Lectins; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D008858:Microscopy, Phase-Contrast; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D017931:DNA Primers; D037483:Galectin 1; D037501:Galectin 2; D037102:Lectins