Divalent cations modulate alpha2beta1 integrin-mediated malignancy in a novel 3-dimensional in vitro model of pancreatic cancer.

Abstract

OBJECTIVES:

We previously showed that divalent cations regulate alpha2beta1 integrin-mediated pancreatic cancer cell interactions with type I collagen in 2 dimensions (2D), including cell adhesion, migration, and proliferation. Presently, we examined divalent cation-dependent alpha2beta1 integrin-mediated pancreatic cancer cell adhesion and proliferation on type I collagen in a novel 3D in vitro model.

METHODS:

Cell attachment, proliferation, and antibody inhibition assays on type I collagen in both 2D and 3D, and microscopy and immunoblotting were used for these studies.

RESULTS:

As in 2D, cell attachment on type I collagen in 3D is Mg-dependent and inhibited by Ca. Proliferation in 3D is also Mg-dependent, but maximal when Mg is present at concentrations that promote maximal cell adhesion and Ca is present at concentrations less than Mg. Immunoblotting studies demonstrate that the divalent cation-dependent changes in cell-cell adhesion observed on type I collagen in both 2D and 3D are associated with the changes in E-cadherin and beta-catenin expression. Antibody inhibition assays indicate further that the alpha2beta1 integrin specifically mediates proliferation on type I collagen in 3D under altered divalent cation conditions.

CONCLUSIONS:

Divalent cation shifts could activate alpha2beta1 integrin-mediated malignancy in the type I collagen-rich 3D tumor microenvironment of pancreatic cancer.

• Authors: John J Grzesiak, Fabian Vargas, Michael Bouvet
• Journal: Pancreas (Pancreas) Vol. 39 Issue 6 Pg. 904-12 (Aug 2010) ISSN: 1536-4828 [Electronic] United States
• PMID: 20182393 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cadherins
• Cations, Divalent
• Collagen Type I
• Integrin alpha2beta1
• beta Catenin
• Magnesium
• Calcium

Topics

• Cadherins (metabolism)
• Calcium (pharmacology)
• Cations, Divalent (pharmacology)
• Cell Adhesion (drug effects)
• Cell Culture Techniques (methods)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Collagen Type I (metabolism)
• Dose-Response Relationship, Drug
• Humans
• Immunoblotting
• Integrin alpha2beta1 (metabolism)
• Magnesium (pharmacology)
• Pancreatic Neoplasms (metabolism, pathology)
• beta Catenin (metabolism)