title: Hypoxia Up-Regulates Galectin-3 in Mammary Tumor Progression and Metastasis.
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.
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology (IPATIMUP), University of Porto, Porto, Portugal; Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), University of Porto, Porto, Portugal; Faculty of Veterinary Medicine of the Lusophone University of Humanities and Technologies, Lisbon, Portugal.
authors.forename: Joana T
authors.initials: JT
authors.lastname: de Oliveira
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology (IPATIMUP), University of Porto, Porto, Portugal.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Ribeiro
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology (IPATIMUP), University of Porto, Porto, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Barros
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology (IPATIMUP), University of Porto, Porto, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Gomes
authors.affiliation: Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), University of Porto, Porto, Portugal; Animal Science and Study Central (CECA), Food and Agrarian Sciences and Technologies Institute (ICETA), University of Porto, Porto, Portugal.
authors.forename: Augusto J
authors.initials: AJ
authors.lastname: de Matos
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology (IPATIMUP), University of Porto, Porto, Portugal; Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
authors.forename: Celso A
authors.initials: CA
authors.lastname: Reis
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands; Specialist Veterinary Centre De Wagenrenk, Utrecht, The Netherlands.
authors.forename: Gerard R
authors.initials: GR
authors.lastname: Rutteman
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology (IPATIMUP), University of Porto, Porto, Portugal; Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
authors.forename: Fátima
authors.initials: F
authors.lastname: Gärtner
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018450:Disease Progression; D004285:Dogs; D005260:Female; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment; D015854:Up-Regulation
chemical_list: D037502:Galectin 3; D051272:Glucose Transporter Type 1; D012333:RNA, Messenger; D012334:RNA, Neoplasm