Clinical & Experimental Metastasis

, Volume 29, Issue 6, pp 561–572

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

Authors

    • School of Medical Science, Griffith Health InstituteGriffith University
  • Stephen J. Ralph
    • School of Medical Science, Griffith Health InstituteGriffith University
Research Paper

DOI: 10.1007/s10585-012-9471-7

Cite this article as:
Ito, K. & Ralph, S.J. Clin Exp Metastasis (2012) 29: 561. doi:10.1007/s10585-012-9471-7

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.

Keywords

Galectin-1Lung metastasisT cellsCancer cell adhesionCD44 and CD326Cancer stem cells

Supplementary material

10585_2012_9471_MOESM1_ESM.tif (1.7 mb)
Supplementary material 1 (TIFF 1747 kb)

Copyright information

© Springer Science+Business Media B.V. 2012