Gastroenterology

Gastroenterology

Volume 115, Issue 2, August 1998, Pages 287-296
Gastroenterology

Alimentary Tract
Metastasis of human colon cancer is altered by modifying expression of the β-galactoside-binding protein galectin 3☆,☆☆

https://doi.org/10.1016/S0016-5085(98)70195-7Get rights and content

Abstract

Background & Aims: Galectin 3 is a β-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.

GASTROENTEROLOGY 1998;115:287-296

Section snippets

Cell lines

Cell line LS174T was derived from a well-differentiated colonic adenocarcinoma and has been characterized extensively.23 It has low metastatic potential in animal models of colon cancer metastasis. LSLiM6 is a derivative of LS174T with high liver-metastasizing ability during cecal growth and liver-colonizing ability after splenic–portal injection in nude mice.23 HM7 is a second variant of LS174T with high liver-metastasizing ability.23 Derivative cell lines transfected with antisense

Galectin 3 expression in human colon cancer cells of different metastatic ability

Cell line LS174T has low spontaneous metastatic potential when grown as cecal xenografts in nude mice and low liver-colonizing ability after inoculation into the splenic-portal system.23 In contrast, cell lines LSLiM6 and HM7, derivatives of LS174T, have high metastatic potential in both of these models.23, 30 Western blot analysis (Figure 1A) showed a significantly higher expression of the 31-kilodalton galectin 3 protein in metastatic cell lines LSLiM6 (8.23-fold ± 4.80-fold, mean ± SD) and

Discussion

Galectins (formerly known as S-type or S-Lac lectins) are a family of carbohydrate-binding proteins identified by conserved amino acid sequences and affinity for β-galactoside–containing glycoconjugates.31 Galectin 3 is a member of the galectin gene family that is expressed at elevated levels in a variety of neoplastic cell types,17, 18, 19, 20, 21, 22 and it has been associated with alterations in cell growth, transformation, and metastasis.1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17

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    ☆

    Address requests for reprints to: Robert S. Bresalier, M.D., Henry Ford Health Sciences Center, 2799 West Grand Boulevard, Detroit, Michigan 48202. Fax: (313) 876-9487.

    ☆☆

    Supported by the Research Service of the Henry Ford Health Sciences Center and Research Foundation (to R.S.B.) and National Cancer Institute grants 1R01CA69480 (to R.S.B.) and 2R01CA46120 (to A.R.).

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    Copyright © 1998 American Gastroenterological Association. Published by Elsevier Inc. All rights reserved.