title: Sialylation regulates galectin-3/ligand interplay during mammary tumour progression--a case of targeted uncloaking.
abstract: Galectin-3 is involved both in facilitating detachment of cells from primary tumour sites and favouring cancer cell adhesion and survival to anoikis in the blood stream. The mechanisms behind these apparently contradictory roles of the lectin have not yet been resolved. In order to investigate possible interplays between galectin-3 and its ligands underlying their role in the metastatic process, we examined mucin-1 (MUC1) and epidermal growth factor receptor (EGFR), well-known galectin-3 ligands, as well as galectin-3-binding site expression in a series of spontaneous canine malignant mammary tumours (CMMT) and a metastatic CMMT cell line. Despite the fact that CMMT cells expressed MUC1 and EGFR homogeneously over their plasma membrane, intravascular tumour cells, positive for galectin-3, expressed MUC1 and EGFR in a more focal membrane localization. Moreover, MUC1 overexpression in primary CMMT was present in parallel with down-regulation of galectin-3. Furthermore, in the CMT-U27 cell line, galectin-3 knock-down led to increased MUC1 expression, while MUC1 knock-down led to down-regulation of the lectin. Finally, removal of sialic acid from both CMMT and CMT-U27 xenograft samples exposed galectin-3-ligands throughout the tumour tissue, whereas these ligands were only present in galectin-3-positive invading cells in untreated samples. Interestingly indeed, we show that in vessel-invading cells, there is interaction between galectin-3 and the T antigen in vivo. We therefore hypothesized that loss of galectin-3 and sialylation-related masking of its ligands, in conjunction with their overexpression in specific tumour cell subpopulations, are crucial in regulating adhesive/de-adhesive events in the progression and invasive capacity of metastatic cells.
authors.affiliation: Institute of Molecular Pathology and Immunology (IPATIMUP), University of Porto, Rua Dr. Roberto Frias s/n, Porto, Portugal.
authors.forename: Joana-Tavares
authors.initials: JT
authors.lastname: de Oliveira
authors.forename: Augusto-José
authors.initials: AJ
authors.lastname: de Matos
authors.forename: Ana L
authors.initials: AL
authors.lastname: Santos
authors.forename: Rita
authors.initials: R
authors.lastname: Pinto
authors.forename: Joana
authors.initials: J
authors.lastname: Gomes
authors.forename: Venceslau
authors.initials: V
authors.lastname: Hespanhol
authors.forename: Roger
authors.initials: R
authors.lastname: Chammas
authors.forename: Aki
authors.initials: A
authors.lastname: Manninen
authors.forename: Emerson S
authors.initials: ES
authors.lastname: Bernardes
authors.forename: Celso
authors.initials: C
authors.lastname: Albuquerque Reis
authors.forename: Gerard
authors.initials: G
authors.lastname: Rutteman
authors.forename: Fátima
authors.initials: F
authors.lastname: Gärtner
mesh_terms: D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism; D001665:Binding Sites; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002470:Cell Survival; D018450:Disease Progression; D004283:Dog Diseases / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D004285:Dogs; D015536:Down-Regulation; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D025461:Feedback, Physiological; D005260:Female; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008024:Ligands; D015674:Mammary Neoplasms, Animal / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D012794:Sialic Acids / Q000378:metabolism; D014183:Transplantation, Heterologous; D015854:Up-Regulation
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D037502:Galectin 3; D008024:Ligands; D018396:Mucin-1; D012794:Sialic Acids; C016467:Thomsen-Friedenreich antigen; D066246:ErbB Receptors