In the present work we have evaluated whether ST3Gal III overexpression and the subsequent changes in the pattern of sialylation have a role in cell-cell adhesiveness and invasion in the MDAPanc-28 and Capan-1 pancreatic cancer cell lines. In addition, we have evaluated the impact of sialylation in the regulation of E-cadherin and a2b1 integrin functions. The human pancreatic adenocarcinoma Capan-1 and MDAPanc-28 ST3Gal III transfected cells have been shown to exhibit a reduced cell-cell Etofibrate aggregation capacity and a high migration and invasion capability when compared with their respective mock cells, which is in agreement with our previous works reporting their increased migration through collagen and in vivo metastatic potential in mice. In addition, Capan-1 cells display higher expression of SLex levels than MDAPanc-28 cells, which consequently show a higher invasive potential and lower aggregation rates than MDAPanc-28. These results reinforce the importance of a 2,3-sialic acid in potentiating cell invasion and metastasis. In accordance, major a 2,3-sialic acid residue expression was associated with higher invasive and metastatic potential of gastric and breast cancer cells and, conversely, Cinchophen decreased a 2,3-sialic acid levels of a lung cancer cell model resulted in invasion and metastasis suppression. Likewise, induction of a more invasive phenotype by the terminal glycan structures containing a 2,3-sialic acid through the activation of invasion-related signaling pathways has been recently reported in gastric carcinoma cells. Pancreatic adenocarcinoma is characterized by a particularly high desmoplasia, and several studies have converged on the hypothesis that type 1 collagen plays an active role in vitro and in vivo in the pathophysiology of this neoplasia. Our results showed that adhesion to type 1 collagen and migration through this ECM protein is dependent on a2b1 integrin in CP and C31 cells, which is in agreement with other reports in pancreatic cancer cell lines. Moreover, we have also shown that a2 and b1 integrins are expressed in the tumor cells and in the desmoplastic stroma of PDAC, in agreement with published studies that describe the expression of a2b1 integrin in pancreatic cancer cells and its interaction with type IV collagen in PDAC tissues.