Oral Presentation Matrix Biology Society of Australia and New Zealand Annual Meeting 2012

Galectin-1 as a Potent Target for Cancer Therapy: Role in the Tumour Microenvironment (#3)

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, Griffith University, Southport, QLD, Australia
  2. Institute for Glycomics, Griffith University, Southport, Queensland, 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 processes within the tumour microenvironment. In the present study, we investigated novel mechanisms for galectin-1-induced immunosuppression, tumour angiogenesis and metastasis, and further examined whether blocking galectin-1 carbohydrate recognition domains (CRDs) using thiodigalactoside (TDG) or knocking down the expression of galectin-1 (G1KD) by shRNA would exhibit tumour suppressive effects. We firstly observed that TDG significantly inhibited galectin-1 binding to the endothelial substratums and surfaces of human endothelial cells associated with reduced endothelial cell proliferation and formation of capillary-like tubes in Matrigel. We further investigated in vivo effects of inhibiting galectin-1 using the B16F10 melanoma, 4T1 breast and CT26 colon carcinoma models. TDG treatment or G1KD significantly reduced tumour angiogenic activities as well as increased both CD4+ Th cell and CD8+ CTL tumour infiltration, resulting in enhanced responses of effector T cells within the tumour microenvironment. In combination with either doxorubicin, anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) mAb (9H10), adenosine receptor (A2AR) antagonist (SCH58261) or B7.1 expressing cancer cell vaccine, galectin-1 inhibition prolonged overall survival of the tumour bearing mice. Moreover, anti-metastatic effects of targeting galectin-1 were also confirmed by using 4T1.2 mCherry+ breast cancer and CT26 colon cancer cell lines. Metastatic foci were significantly reduced by either TDG or shRNA galectin-1 knockdown (G1KD), associated with increased CD4+ and CD8+ T cell levels in the peripheral blood. Interestingly, the expression of cancer stem cell markers, CD44 and CD326 in breast and colon cancer and CD271 and ABCB5 in melanoma were correlated with galectin-1 expression in the metastatic lesions, suggesting an association of galectin-1 with cancer stem cells. In conclusion, the present study confirmed that targeting galectin-1 could represent a novel and effective anti-cancer and anti-metastatic strategy.