Abstract
The tumor microenvironment encompasses several stressful conditions for cancer cells such as hypoxia, oxidative stress and pH alterations. Galectin-3, a well-studied member of the beta-galactoside-binding animal family of lectins has been implicated in multiple steps of metastasis as cell-cell and cell-ECM adhesion, promotion of angiogenesis, cell proliferation and resistance to apoptosis. However, both its aberrantly up- and down-regulated expression was observed in several types of cancer. Thus, the mechanisms that regulate galectin-3 expression in neoplastic settings are not clear. In order to demonstrate the putative role of hypoxia in regulating galectin-3 expression in canine mammary tumors (CMT), in vitro and in vivo studies were performed. In malignant CMT cells, hypoxia was observed to induce expression of galectin-3, a phenomenon that was almost completely prevented by catalase treatment of CMT-U27 cells. Increased galectin-3 expression was confirmed at the mRNA level. Under hypoxic conditions the expression of galectin-3 shifts from a predominant nuclear location to cytoplasmic and membrane expressions. In in vivo studies, galectin-3 was overexpressed in hypoxic areas of primary tumors and well-established metastases. Tumor hypoxia thus up-regulates the expression of galectin-3, which may in turn increase tumor aggressiveness.
Highlights
Galectin-3 is a unique member of the family of galectins
We propose a model to reconcile the overexpression of galectin-3 in necrosis surrounding areas of canine mammary cancer lesions and suggest that this might be a critical player in metastasis
In order to assess a possible regulation of galectin-3 by hypoxia in neoplastic settings, we used a highly metastatic canine mammary cancer cell line, canine mammary tumors (CMT)-U27
Summary
Galectin-3 is a unique member of the family of galectins. It is a carbohydrate-binding protein which mediates cell—cell and cell—extracellular matrix (ECM) interactions and that has been implicated in several key steps of the cancer metastatic process [1, 2] and drug resistance [3, 4].PLOS ONE | DOI:10.1371/journal.pone.0134458 July 29, 2015Galectin-3 Is Up-Regulated by Hypoxia in Mammary TumorsScience, Technology and Higher Education and is partially supported by the Portuguese Foundation for Science and Technology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
