Upregulation of galectins-1 and-3 in human colon cancer and their role in regulating cell migration

被引:141
作者
Hittelet, A
Legendre, H
Nagy, N
Bronckart, Y
Pector, JC
Salmon, I
Yeaton, P
Gabius, HJ
Kiss, R
Camby, I
机构
[1] Free Univ Brussels, Fac Med, Lab Histopathol, B-1070 Brussels, Belgium
[2] Free Univ Brussels, Erasme Hosp, Lab Gastroenterol, B-1050 Brussels, Belgium
[3] Inst Jules Bordet, Dept Surg, B-1000 Brussels, Belgium
[4] Free Univ Brussels, Erasme Hosp, Lab Anatomopathol, B-1050 Brussels, Belgium
[5] Univ Virginia, Digest Hlth Ctr, Charlottesville, VA USA
[6] Univ Munich, Fac Vet Med, Inst Physiol Chem, Munich, Germany
关键词
colon cancer; dysplasia; galectin-1; galectin-3; integrin; in vitro cell line; in vivo xenograft; cell migration;
D O I
10.1002/ijc.10843
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
To probe the potential contribution of P-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 mug/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. (C) 2002 Wiley-Liss, Inc.
引用
收藏
页码:370 / 379
页数:10
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