Cytokines modulate MIA PaCa 2 and CAPAN-1 adhesion to extracellular matrix proteins.

Variations in cancer cell adhesion to extracellular matrix (ECM) proteins might underlie an enhanced metastatic potential. ECM binding is mediated by cell-adhesion molecules, the membrane expression of which might be influenced by soluble mediators, such as cytokines. The aims of our study were to ascertain whether epidermal growth factor (EGF), transforming growth factor beta 1 (TGF-beta 1), interleukin 1 alpha (IL-1 alpha), or interleukin 1 beta (IL-1 beta) can modify MIA PaCa 2 (pancreatic cancer cell line) and CAPAN-1 (metastatic pancreatic cancer cell line) adhesion to fibronectin, laminin, or type I collagen, and whether these cytokines can shift the membrane expression of the hyaluronic acid receptor (CD44). EGF significantly enhanced MIA PaCa 2, but not CAPAN-1, adhesion to fibronectin, laminin, and type I collagen. TGF-beta 1 reduced MIA PaCa 2 adhesion to type I collagen, but enhanced CAPAN-1 adhesion to fibronectin and laminin. IL-1 alpha was found to enhance MIA PaCa 2 adhesion to fibronectin, while reducing adhesion to type I collagen, whereas IL-1 beta reduced the adhesion to laminin. IL-1 alpha enhanced CAPAN-1 adhesion to laminin in a dose-dependent manner; IL-1 beta slightly increased the adhesion of these cells to laminin at low dosage, and to type I collagen at high dosage. Both IL-1 alpha and IL-1 beta reduced CD44 membrane expression of MIA PaCa 2, while TGF-beta 1 increased the percentage of CD44-positive CAPAN-1 cells. We suggest that,the effects on cell adhesion induced by different cytokines depend on the status of the target pancreatic cancer cell. EGF and, in art, IL-1 alpha. can favor nonmetastatic pancreatic cancer cell adhesion to ECM, possibly favoring tumor spread. Metastatic cells seem to lose the responsiveness to EGF, while becoming hyperresponsive to IL-1 alpha. TGF-beta 1 might exert an antidiffusive effect on primary, and a prodiffusive effect on metastatic pancreatic cancer cells. Only IL-1 alpha, IL-1 beta, and TGF-beta 1 seem to influence CD44 membrane expression. All the results presented in this study were obtained in vitro, and in vivo studies are needed to verify whether the studied cytokines can favor or counteract: pancreatic cancer spread.