Pharmacogenomics - PhD and honours Projects - Galectin-3 and breast cancer metastasis

Galectin-3 and breast cancer metastasis

Project Type

PhD

Summary

A number of prior studies support the prominent role of Galectin-3 (Gal-3) in cancer progression and metastasis. This includes 1) the reversal of malignancy with Gal-3 antisense transfection, 2) reduction of tumour growth and metastasis in mice with modified citrus pectin (which inhibits Gal-3), 3) established role of Gal-3 in modulating adhesive properties of breast carcinoma cells, 4) an anti-apoptotic role in promoting tumour cell survival. Furthermore, we have evidence that matrix metalloproteinase (MMP-) cleaved Gal-3 selectively stimulates breast cancer cell migration. Our hypothesis is that MMP-mediated cleavage is required for the pro-metastatic properties of Gal-3.

For this project, the student will modulate Galectin-3 expression levels in different human breast cancer cell lines, using transfection and siRNA, and look at the consequences on metastasis to soft organs and breast-bone metastasis. In addition, specific domains in the Gal-3 molecule will be tested, as well as the role of MMP-mediated cleavage of the Gal-3 amino terminal domain. Specific blocking of Gal-3 and MMP-processed Gal-3 may open a new potential therapeutic strategy to combat cancer metastasis.