Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

Galectin-1 as a Potent Target for Cancer and Metastasis Therapy: Role in the Tumour Microenvironment (#167)

Koichi Ito 1 2 , Selda Onturk 1 , Michael Lousick 1 , Shi-Yong Neo 1 , Helen Blanchard 2 , Stephen J. Ralph 1
  1. Griffith Health Institute, Southport, QLD, Australia
  2. Institute for Glycomics, Griffith University, Southport, QLD, Australia

Galectin-1 is a hypoxia-inducible beta-galactoside binding lectin protein produced by a wide range of cancer cells and plays a number of significant roles within the tumour microenvironment. This includes immunosuppression, pro-angiogenesis, promotion of cell adhesion and metastasis. Higher levels of galectin-1 and galectin-1 bound glycoproteins in plasma of cancer patients were reported to correspond with poor diagnosis and high risk of metastasis. It was first demonstrated that blocking galectin-1 carbohydrate recognition domains (CRDs) using thiodigalactoside (TDG) or knocking down the expression of galectin-1 (G1KD) by shRNA exhibited tumour suppressive effects in primary B16F10 melanoma, 4T1 breast cancer and CT26 colon cancer models in mice1. This was associated with reduced tumour angiogenic activities and increased T cell infiltration into the tumours. Anti-metastatic effects of targeting galectin-1 were also investigated by using the 4T1.2 mCherry+ and CT26 cell lines. The numbers and size of metastatic foci were significantly reduced by either TDG or G1KD, associated with increased CD4+ and CD8+ T cell levels in the peripheral blood and TUNEL+mCherry+ cells in the lung, indicating higher levels of targeted metastatic cell death2 . Moreover, galectin-1 was found to bind to cancer-initiating cell (CIC) markers, CD44 and CD326, in 4T1 cells by co-immunoprecipitation assay2. Inhibiting galectin-1 significantly reduced its binding to CD44 and CD326, leading to suppressed 4T1 cell attachment onto endothelium substrata, including laminin, Matrigel and human endothelial EAhy926 cells2. More recent data implicate a further significant role of galectin-1 in CIC biology, which is important to understand a metastatic process. In conclusion, the present study confirms that targeting galectin-1 represents a novel and effective anti-cancer and anti-metastatic strategy in different types of cancers.

  1. K.Ito et al, Angiogenesis, 2011.
  2. K.Ito et al, Clin Exp Metastasis, 2012.
  3. K.Ito et al, Cancer Metastasis Rev, 2012.