Activation of the α2β1 integrin-mediated malignant phenotype on type I collagen in pancreatic cancer cells by shifts in the concentrations of extracellular Mg2+ and Ca2+
✍ Scribed by John J. Grzesiak; Michael Bouvet
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- French
- Weight
- 755 KB
- Volume
- 122
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
The authors have previously demonstrated that α~2~β~1~ integrin‐mediated pancreatic cancer cell adhesion to Type I collagen is Mg^2+^‐dependent, inhibited by Ca^2+^, and that this integrin, purified from cell lysates using Type I‐collagen‐sepharose in Mg^2+^, can be eluted with Ca^2+^. In the present study, the authors examined the divalent cation‐dependency of α~2~β~1~ integrin‐mediated pancreatic cancer cell adhesion, migration and proliferation on Type I collagen, an extracellular matrix protein shown to be highly up‐regulated, and to promote the malignant phenotype in vitro and in vivo. The results indicate that cells attach to Type I collagen maximally when Mg^2+^ is greater than 1 mM, and that addition of increasing concentrations of Ca^2+^ reduces this adhesion. These effects are reversible, in that previous cell attachment in Mg^2+^ can be reversed by adding Ca^2+^, and vice versa. They also demonstrate that pancreatic cancer cells migrate and proliferate on Type I collagen in Mg^2+^ alone, but maximally when Mg^2+^ is present at concentrations that promote maximal cell adhesion and Ca^2+^ is present at concentrations less than Mg^2+^. Cell adhesion and proliferation assays, as well as affinity chromatography on Type I collagen using anti‐integrin function‐blocking monoclonal antibodies indicate that the effects of these divalent cation shifts are mediated specifically by the α~2~β~1~ integrin. As pancreatic juice contains over 1,200‐fold more Mg^2+^ than Ca^2+^ and solid tumors are characterized by increased magnesium load, these data indicate that such pathophysiological divalent cation shifts could be involved in the activation of the α~2~β~1~ integrin‐mediated malignant phenotype on Type I collagen in the pancreatic cancer. © 2008 Wiley‐Liss, Inc.