Galectin-3 Regulates the Expression of Tumor Glycosaminoglycans and Increases the Metastatic Potential of Breast Cancer

Abstract

Galectin-3 (Gal-3) is a multifunctional β-galactoside-binding lectin that once synthesized is expressed in the nucleus, cytoplasm, cell surface, and extracellular environment. Gal-3 plays an important role in breast cancer tumors due to its ability to promote interactions between cell-cell and cell-extracellular matrix (ECM) elements, increasing tumor survival and metastatic dissemination. Still, the mechanism by which Gal-3 interferes with tumor cell migration and metastasis formation is complex and not fully understood. Here, we showed that Gal-3 knockdown increased the migration ability of 4T1 murine breast cancer cells in vitro. Using the 4T1 orthotopic breast cancer spontaneous metastasis mouse model, we demonstrated that 4T1-derived tumors were significantly larger in the presence of Gal-3 (scramble) in comparison with Gal-3 knockdown 4T1-derived tumors. Nevertheless, Gal-3 knockdown 4T1 cells were outnumbered in the bone marrow in comparison with scramble 4T1 cells. Finally, we reported here a decrease in the content of cell-surface syndecan-1 and an increase in the levels of chondroitin sulfate proteoglycans such as versican in Gal-3 knockdown 4T1 cells both in vitro and in vivo. Overall, our findings establish that Gal-3 downregulation during breast cancer progression regulates cell-associated and tumor microenvironment glycosaminoglycans (GAGs)/proteoglycans (PG), thus enhancing the metastatic potential of tumor cells.

Integrated Bioinformatics Analysis Reveals Key Candidate Genes and Pathways Associated With Clinical Outcome in Hepatocellular Carcinoma

“…Recent studies have shown that LGALS3 is tightly associated with several malignancies such as Hodgkin’s lymphoma ( Koh et al, 2014 ), acute myeloid leukemia ( Cheng et al, 2013 ), and HCC ( Song et al, 2014 ). More importantly, LGALS3 could increase the metastatic potential of breast cancer, might accounting for the metastatic potential of HCC ( Pereira et al, 2019 ). Through validation in western blot and IHC assays, we found that the protein expression of these five hub genes was in accordance with their mRNA expression in HCC patient tissues.…”

Galectins as pivotal components in oncogenesis and immune exclusion in human malignancies

“…Both experiments showed that intracellular Gal-3 tends to reduce the metastatic potential of B16 cells, at least in part by negative regulation of the integrin-b3 (94). In contrast, working with the 4T1 murine breast carcinoma model, Pereira et al showed that Gal-3 tends to increase the metastatic potential of these malignant cells with a concomitant reduction of the surface expression of syndecan-1 and a greater expression of chondroitin sulfate proteoglycans such as versican (95). Apparently with regard to Gal-1, published data are more consistent suggesting that it frequently enhances the metastatic potential of malignant cells.…”

Insights into the role of sialylation in cancer progression and metastasis

“…Elevated levels of Gal-3 are typically associated with a pro-metastatic tumour phenotype; however, Pereira et al have reported that reduced Gal-3 expression during breast cancer progression correlated with increased metastasis of 4T1 murine breast cancer cells to the bone marrow. 77 …”