title: Divalent cations modulate the integrin-mediated malignant phenotype in pancreatic cancer cells.
abstract: We have previously demonstrated that pathophysiological shifts in the concentrations of extracellular Mg(2+) and Ca(2+) activate the alpha(2)beta(1) integrin-mediated malignant phenotype on type I collagen in pancreatic cancer cells, as evidenced by increased adhesion, migration and proliferation. In the present study, we examined the integrin and divalent cation specificity of pancreatic cancer cell interactions with other physiologically relevant extracellular matrix proteins, including fibronectin, type IV collagen, laminin and vitronectin. Our results indicate that, like alpha(2)beta(1) integrin-mediated interactions with type I collagen, beta(1) integrin-mediated adhesion to fibronectin, type IV collagen and laminin are promoted by Mg(2+) but not by Ca(2+). On vitronectin, cells attach via alpha(v)beta(5) and beta(1) integrins, and in the presence of either divalent cation. We also demonstrate that, like type I collagen, pancreatic cancer cell migration and proliferation on fibronectin, laminin and type IV collagen is maximal when Mg(2+) is present at concentrations that promote optimal adhesion and Ca(2+) is present at concentrations less than Mg(2+). On vitronectin, Panc-1 cell migration is maximal with decreased Mg(2+) and increased Ca(2+), but the reverse is true for BxPC-3 cells. Both cell lines exhibited maximal proliferation with increased Mg(2+) and decreased Ca(2+), however. Together with evidence indicating that the in vivo local tumor microenvironment contains increased Mg(2+) and decreased Ca(2+), our studies demonstrate that such divalent cation shifts could activate the integrin-mediated malignant phenotype in pancreatic cancer.
authors.affiliation: Department of Surgery, University of California, Veterans Affairs San Diego Healthcare System, San Diego, California 92161, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Grzesiak
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet