Coordinated expression of galectin-3 and galectin-3-binding sites in malignant mammary tumors: implications for tumor metastasis

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Joana Tavares de Oliveira (Author) Other; Augusto J F de Matos (Author) ICBAS; Joana Gomes (Author) Other; Manuel Vilanova (Author) ICBAS; Venceslau Hespanhol (Author) Other; Aki Manninen (Author) Other; Gerard Rutteman (Author) Other; Roger Chammas (Author) Other; Fatima Gaertner (Author) Other; Emerson Soares Bernardes (Author) Other

Journal

Title: Glycobiology

Vol. 20 No. 11

Pages: 1341-1352

ISSN: 0959-6658

Publisher: Oxford University Press

Indexing

ISI Web of Knowledge - 22 Citations

Scopus - 24 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: P-003-1CH

DOI: 10.1093/glycob/cwq103

Abstract (EN): 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 beta (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 de-creased 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12