In previous studies we have described that a2,3-sialyltransferase ST3Gal III transfection of pancreatic adenocarcinoma cell lines Capan-1 and MDAPanc-28 leads to the overexpression of SLex antigen and the decrease of a2,6-sialic acid in their cell surface. ST3Gal III BM-1074 transfectants exhibited loss of cell-ECM adhesion, increased motility rates through type 1 BAY 80-6946 collagen and an enhanced metastatic phenotype in vivo. To understand this enhanced metastatic phenotype in vivo, we here address whether cell-cell adhesiveness and cell invasion are also affected by the cell sialylation changes using the stably transfected cell line models. We have also determined whether the cell surface glycan differences between transfected and control cells could be displayed in their a2b1 integrin and E-cadherin molecules and could thus modulate their function. The local microenvironment provides tissues with extrinsic barriers to limit the outgrowth of tumors at the primary site. But as tumors evolve, these pressures drive the selection for traits that enable cancerous cells to by-pass them. Dissemination of carcinomas from their original sites of development to distant organs in the body is the cause for the major part of cancer morbidity and mortality. Although the molecular mechanisms underlying the cellular changes that take place during the invasive process are still not fully understood, there is a general consensus that cell-cell and cell-matrix interactions have to be profoundly altered. In fact, homophilic cell adhesion and integrin signaling are among the core signaling pathways that are altered in most pancreatic cancers, including genetically altered genes such as E-cadherin and integrins. In previous studies we have demonstrated the influence of sialic acid determinants in cell-ECM adhesion and in migratory processes of various human cancer models, including gastric cancer cells, and in pancreatic Capan-1 and MDAPanc-28 cell lines and their stably ST3Gal III transfected clones, C31 and M34. Specifically, cell surface a2,6-sialic acid levels correlated with higher cell adhesion to ECM components, such as collagen, fibronectin and laminin, which are important components of the tumor stroma, while higher a2,3-sialic acid levels favored migration and metastasis.