Pancreatic Cancer Cell Glycosylation Regulates Cell Adhesion and Invasion through the Modulation of [alpha]2[beta]1 Integrin and E-Cadherin Function

• Published in: PloS one 2014-05, Vol.9 (5)
• Main Authors: Bassagañas, Sònia, Carvalho, Sandra, Dias, Ana M, Pérez-Garay, Marta, Ortiz, M. Rosa, Figueras, Joan, Reis, Celso A, Pinho, Salomé S, Peracaula, Rosa
• Format: Article
• Language: English
• Subjects: Collagen; Integrins; Pancreatic cancer
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0098595

In our previous studies we have described that ST3Gal III transfected pancreatic adenocarcinoma Capan-1 and MDAPanc-28 cells show increased membrane expression levels of sialyl-Lewis x (SLe.sup.x) along with a concomitant decrease in [alpha]2,6-sialic acid compared to control cells. Here we have addressed the role of this glycosylation pattern in the functional properties of two glycoproteins involved in the processes of cancer cell invasion and migration, [alpha]2[beta]1 integrin, the main receptor for type 1 collagen, and E-cadherin, responsible for cell-cell contacts and whose deregulation determines cell invasive capabilities. Our results demonstrate that ST3Gal III transfectants showed reduced cell-cell aggregation and increased invasive capacities. ST3Gal III transfected Capan-1 cells exhibited higher SLe.sup.x and lower [alpha]2,6-sialic acid content on the glycans of their [alpha]2[beta]1 integrin molecules. As a consequence, higher phosphorylation of focal adhesion kinase tyrosine 397, which is recognized as one of the first steps of integrin-derived signaling pathways, was observed in these cells upon adhesion to type 1 collagen. This molecular mechanism underlies the increased migration through collagen of these cells. In addition, the pancreatic adenocarcinoma cell lines as well as human pancreatic tumor tissues showed colocalization of SLe.sup.x and E-cadherin, which was higher in the ST3Gal III transfectants. In conclusion, changes in the sialylation pattern of [alpha]2[beta]1 integrin and E-cadherin appear to influence the functional role of these two glycoproteins supporting the role of these glycans as an underlying mechanism regulating pancreatic cancer cell adhesion and invasion.