Galectin-3, a secreted protein that acts via a pro-apoptotic mechanism, as a potential therapeutic for the treatment of cancer.
- Gal-3 inhibits tumor cell growth in vitro by inducing cell apoptosis, while normal cells are unaffected.
- Gal-3 strongly reduces tumor formation in vivo.
- Gal-3 secretion can be modulated in a p53-dependent manner.
Gal-3 is a beta-galactoside binding protein that performs different functions based on its cellular localization. As an extracellular secreted protein, Gal-3 can play a pro-apoptotic role. Gal-3 secretion is facilitated by p53 transcriptional activation of TSAP6, a transmembrane protein that plays a key role in protein secretion by exosomes. p53 itself can exert cell extrinsic control over tumor formation through the modulation of a cellular secretome, including the secretion of Gal-3.
The regulation by p53 of the anti-tumor activities of extracellular Gal-3 represents a new paracrine pro-apoptotic and tumor suppressive function of p53 and provides a novel molecular mechanism for p53 mediated bystander effects in anti-cancer treatment. The composition of the secretome can also provide indicators useful in the diagnosis and prognosis of disease, a system for development and identification of biomarkers in tumor biology, as well as potential therapeutic targets for cancer therapies.
A potential biomarker has been identified for cancers that would respond well to Gal-3 treatment.