Activation of the alpha2beta1 integrin-mediated malignant phenotype on type I collagen in pancreatic cancer cells by shifts in the concentrations of extracellular Mg2+ and Ca2+.

Abstract

The authors have previously demonstrated that alpha(2)beta(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 alpha(2)beta(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 alpha(2)beta(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 alpha(2)beta(1) integrin-mediated malignant phenotype on Type I collagen in the pancreatic cancer.

• Authors: John J Grzesiak, Michael Bouvet
• Journal: International journal of cancer (Int J Cancer) Vol. 122 Issue 10 Pg. 2199-209 (May 15 2008) ISSN: 1097-0215 [Electronic] United States
• PMID: 18224679 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2008 Wiley-Liss, Inc.

Chemical References

• Collagen Type I
• Integrin alpha2beta1
• Magnesium
• Calcium

Topics

• Calcium (metabolism)
• Cell Adhesion (physiology)
• Cell Movement
• Cell Proliferation
• Chromatography, Affinity
• Collagen Type I (metabolism)
• Humans
• Immunoblotting
• Integrin alpha2beta1 (metabolism)
• Magnesium (metabolism)
• Pancreatic Neoplasms (metabolism, pathology)
• Phenotype
• Tumor Cells, Cultured