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.