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Inhibiting galectin-1 reduces murine lung metastasis with increased CD4+ and CD8+ T cells and reduced cancer cell adherence

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Abstract

Galectin-1 is a β-galactoside-binding protein overexpressed by cancer cells. The primary roles of galectin-1 in cancer progression and metastasis are attributed to suppression of T cell immune responses, promotion of tumor angiogenesis and increased tumor cell adhesion and invasion. Using pulmonary metastasis models of murine breast (4T1) and colon (CT26) cancer, we demonstrate that targeting galectin-1 with thiodigalactoside (TDG) or shRNA galectin-1 knockdown (G1KD) results in a significant reduction in lung metastasis. Increased numbers of CD4+ helper T cells and CD8+ cytotoxic T lymphocytes were found in the peripheral blood of both TDG-treated and G1KD cell challenged mice. The levels of TUNEL+ apoptotic cancer cells and the presence of CD3+ T cells were also increased in lung metastases. Furthermore, galectin-1 was found to bind to the adhesion molecules, CD44 and CD326, which are also known as markers of breast and colon cancer stem cells, and TDG likely blocks galectin-1 binding to these molecules. The TDG-mediated inhibition of galectin-1 binding reduced 4T1 cell adhesion to the basement membrane protein laminin, Matrigel and EAhy926 endothelial cell surfaces. These findings establish possible mechanisms for the anti-metastatic effect of galectin-1 inhibition and suggest that targeting galectin-1 may represent a promising and effective anti-metastatic therapy.

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Acknowledgments

The authors acknowledge Dr Robin Anderson, Peter MacCallum Cancer Centre, for providing us the 4T1.2 mCherry+ cell line. We thank Dr Helen Blanchard, the Institute for Glycomics Griffith University, for contribution to recombinant galectin-1 purification. We also thank Dr. Elwyn Gabutero, Dr Andy Wu and Miss Amanda Clark for the manuscript editing. Finally, we thank Dr Adrian Meedeniya and Dr Cameron Flegg, Griffith Imaging Facility, for technical supports in microscopy.

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  1. School of Medical Science, Griffith Health Institute, Griffith University, Gold Coast Campus, Southport, QLD, 4222, Australia

    Koichi Ito & Stephen J. Ralph

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  1. Koichi Ito
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Correspondence to Koichi Ito.

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Ito, K., Ralph, S.J. Inhibiting galectin-1 reduces murine lung metastasis with increased CD4+ and CD8+ T cells and reduced cancer cell adherence. Clin Exp Metastasis 29, 561–572 (2012). https://doi.org/10.1007/s10585-012-9471-7

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  • DOI: https://doi.org/10.1007/s10585-012-9471-7

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