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

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.
AuthorsKoichi Ito, Stephen J Ralph
JournalClinical & experimental metastasis (Clin Exp Metastasis) Vol. 29 Issue 6 Pg. 561-72 (Aug 2012) ISSN: 1573-7276 [Electronic] Netherlands
PMID22484915 (Publication Type: Journal Article)
Chemical References
  • Antigens, Neoplasm
  • Cell Adhesion Molecules
  • Drug Combinations
  • Epithelial Cell Adhesion Molecule
  • Galectin 1
  • Hyaluronan Receptors
  • Laminin
  • Proteoglycans
  • matrigel
  • Collagen
Topics
  • Animals
  • Antigens, Neoplasm (biosynthesis)
  • CD4-Positive T-Lymphocytes (metabolism)
  • CD8-Positive T-Lymphocytes (metabolism)
  • Cell Adhesion
  • Cell Adhesion Molecules (biosynthesis)
  • Cell Line, Tumor
  • Collagen (chemistry)
  • Drug Combinations
  • Epithelial Cell Adhesion Molecule
  • Female
  • Galectin 1 (biosynthesis)
  • Humans
  • Hyaluronan Receptors (biosynthesis)
  • In Situ Nick-End Labeling
  • Laminin (chemistry)
  • Lung Neoplasms (metabolism)
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Proteoglycans (chemistry)

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