title: Coordinated expression of galectin-3 and galectin-3-binding sites in malignant mammary tumors: implications for tumor metastasis.
abstract: Galectin-3 is a glycan-binding protein that mediates cell-cell and/or cell-extracellular matrix (ECM) interactions. Although galectin-3 is implicated in the progression of various types of cancers, the mechanisms by which galectin-3 enhances metastasis remain unclear. In order to elucidate the role of galectin-3 in the complex multistage process of cancer metastasis, we examined galectin-3 and galectin-3-binding site expression in a series of 82 spontaneous canine mammary tumors (CMT) and two CMT cell lines. Benign CMT tumors exhibited strong nuclear/cytoplasmic galectin-3 immunostaining, whereas malignant CMT tumors and metastases exhibited dramatically decreased galectin-3 expression with the majority of the immunostaining confined to the cytoplasm. Interestingly, intravascular tumor cells overexpressed galectin-3 regardless of their location. CMT-U27 xenografts displayed the same pattern of galectin-3 expression found in spontaneous malignant CMT. In parallel with the downregulation of galectin-3, malignant CMT displayed an overall loss of galectin-3-binding sites in the ECM and focal expression of galectin-3-binding sites mainly detected in intravascular tumor cells and endothelium. Furthermore, loss of galectin-3-binding sites was correlated with the downregulation of GLT25D1, a β (1-O) galactosyltransferase that modifies collagen, and upregulation of stromal galectin-1. Finally, GLT25D1 mRNA expression was strikingly downregulated in malignant CMT-U27 compared with the benign cell line, and its expression was further decreased in a galectin-3 knockdown CMT-U27 cell line. We therefore hypothesized that the loss of galectin-3-binding sites in the ECM in conjunction with the overexpression of galectin-3 in specific tumor cell subpopulations are crucial events for the development of mammary tumor metastases.
authors.affiliation: Institute of Molecular Pathology and Immunology (IPATIMUP), University of Porto, Porto, Portugal.
authors.forename: Joana Tavares
authors.initials: JT
authors.lastname: de Oliveira
authors.forename: Augusto Jf
authors.initials: AJ
authors.lastname: de Matos
authors.forename: Joana
authors.initials: J
authors.lastname: Gomes
authors.forename: Manuel
authors.initials: M
authors.lastname: Vilanova
authors.forename: Venceslau
authors.initials: V
authors.lastname: Hespanhol
authors.forename: Aki
authors.initials: A
authors.lastname: Manninen
authors.forename: Gerard
authors.initials: G
authors.lastname: Rutteman
authors.forename: Roger
authors.initials: R
authors.lastname: Chammas
authors.forename: Fátima
authors.initials: F
authors.lastname: Gärtner
authors.forename: Emerson Soares
authors.initials: ES
authors.lastname: Bernardes
mesh_terms: D000818:Animals; D001665:Binding Sites; D002471:Cell Transformation, Neoplastic; D004285:Dogs; D015536:Down-Regulation; D005260:Female; D037502:Galectin 3 / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D014183:Transplantation, Heterologous
chemical_list: D037502:Galectin 3