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^x) 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 SLe^x 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 SLe^x 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.

We report the case of a 19-year-old woman who presented with a hepatic mass without cirrhosis. Light microscopy revealed a cholangiocarcinoma having both well-differentiated adenocarcinoma and lymphoepithelioma-like undifferentiated carcinoma components. By immunohistochemistry, the tumor showed strong and diffuse expression for cytokeratin AE1, 5D3, and CK22. The tumor cells were positive for p53 protein (more than 75% of the cells) but negative for bcl-2 and LMP-1. Abundant Epstein-Barr virus EBER 2 oligonucleotides were detected in both tumor components, but not in the lymphoid stroma or the nontumor liver. To the best of our knowledge, this is the third report of an Epstein-Barr virus-associated primary hepatobiliary adenocarcinoma with lymphoepithelioma-like component.