Galectin-3 increases the motility of mouse melanoma cells by regulating matrix metalloproteinase-1 expression

Although mounting evidence indicates the involvement of galectin-3 in cancer progression and metastasis, the underlying molecular mechanisms remain largely unknown. In this study, we investigated the effect and possible mechanism of galectin-3 on the migration and invasion of B16F10, a metastatic melanoma cell line, in which galectin-3 and matrix metalloproteinase-1 (MMP-1) were both found to be highly expressed. Knockdown of galectin-3 with specific siRNA reduced migration and invasion, which was associated with reduced expression of MMP-1. To further investigate the underlying mechanism, we examined the effect of galectin-3 knockdown on the activity of AP-1, a transcriptional factor regulating MMP-1 expression. We found that galectin-3 directly interacted with AP-1 and facilitated the binding of this complex to the MMP-1 promoter that drives MMP-1 transcription. Moreover, silencing of galectin-3 inhibited binding of fra-1 and c-Jun to promoter sites of MMP-1 gene. Consistent with these in vitro findings, our in vivo study demonstrated that galectin-3 shRNA treatment significantly reduced the total number of mouse lung metastatic nodules. Taken together, galectin-3 facilitates cell migration and invasion in melanoma in vitro and can induce metastasis in vivo, in part through, regulating the transcription activity of AP-1 and thereby up-regulating MMP-1 expression.

Impact of galectin-3 deficiency on gene expression in the liver of mice 48-h post-treatment with olive oil or CC1[4]

Galectin-3 [Gal-3] is a multifunctional protein, playing a key role in many biolegical processes. Previous study demonstrated that normal hepatocytes do not express galectin-3, but this protein can be present in injured liver. The present paper aimed to assist in elucidate the biological role of galectin-3 in injured liver by CC1[4] and to clarify genes that differentially expressed in response to galectin-3 deficiency in normal and chemically injured liver of mice 48-h post-treatment with olive oil or CC1[4]. Four male wild type mice [WT] and another four galectin-3 disrupted mice [Gal-3[-/-]] were used in this experiment. The mice were fasted overnight and classified into two groups, [each group including, two WT and two Gal-3[-/-] mice] the first subgroup received in the following morning 4 ml/kg olive oil, while the second subgroup was received 8 ml/kg CC1[4] [50% in olive oil] by gavages. After 48h, the mice were anesthetized and killed to obtain blood and excise the liver. Gene's expression analysis in the liver tissue was carried out using cDNA microarray technique. The cDNA microarrays analysis revealed that 7 genes have clearly changed their levels of expression, of these 5 genes related to detoxification mechanisms are up-regulated and 2 genes related to tumor cell and amyloid protein have been down-regulated in Gal-3[-/-] mice after 48 h post-treatment with olive oil. The mice treated with CC1[4] reveled that 42 genes have clearly changed their levels of expression, of this 8 genes were up-regulated and 34 genes were down-regulated. Of the up-regulated genes were detoxification, fatty acids and lipid metabolism proteins. On the other hand, the down-regulated genes encoded proteins for xenobiotic metabolism, stress response, transcription factors, lipid metabolism, proteolysis and peptedolysis, RNA, nerve system, and immune responses proteins. This study demonstrated that changes in gene expression profile in galectin-3 deficiency mice 48-h post-treatment with CC1[4], mostly related to down-regulated different genes including, many biological processes, implying the multifunctional of galectin-3 to protect and ameliorated the liver injury induced by CC1[4] in mice