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Pancreatic Cancer Cell Glycosylation Regulates Cell Adhesion and Invasion through the Modulation of a2b1 Integrin and E-Cadherin Function

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 (SLex) along with a concomitant decrease in α2,6-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, α2β1 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 SLex and lower α2,6-sialic acid content on the glycans of their α2β1 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 SLex and E-cadherin, which was higher in the ST3Gal III transfectants. In conclusion, changes in the sialylation pattern of α2β1 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

PLoS One, vol. 9, núm. 5, p. e98595

Public Library of Science (PLoS)

Author: Bassagañas i Puigdemont, Sònia
Carvalho, Sandra
Dias, Ana M.
Pérez Garay, Marta
Ortiz, Maria Rosa
Figueras, Joan
Reis, Celso A.
Pinho, Salomé S.
Peracaula Miró, Rosa
Date: 2014
Abstract: 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 (SLex) along with a concomitant decrease in α2,6-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, α2β1 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 SLex and lower α2,6-sialic acid content on the glycans of their α2β1 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 SLex and E-cadherin, which was higher in the ST3Gal III transfectants. In conclusion, changes in the sialylation pattern of α2β1 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
Format: application/pdf
Citation: 020822
ISSN: 1932-6203
Document access: http://hdl.handle.net/10256/10406
Language: eng
Publisher: Public Library of Science (PLoS)
Collection: Reproducció digital del document publicat a: http://dx.doi.org/10.1371/journal.pone.0098595
Articles publicats (D-B)
Is part of: PLoS One, vol. 9, núm. 5, p. e98595
Rights: Attribution 3.0 Spain
Rights URI: http://creativecommons.org/licenses/by/3.0/es/
Subject: Pàncrees -- Càncer
Pancreas -- Cancer
Glicosilació
Glycosylation
Title: Pancreatic Cancer Cell Glycosylation Regulates Cell Adhesion and Invasion through the Modulation of a2b1 Integrin and E-Cadherin Function
Type: info:eu-repo/semantics/article
Repository: DUGiDocs

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