Metastasis of human colon cancer is altered by modifying expression of the beta-galactoside-binding protein galectin 3.

Abstract

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. 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. 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. This study provides direct evidence that galectin 3 plays an important role in colon cancer metastasis.