二价阳离子调节新型胰腺癌三维体外模型中α2β1 整合素介导的恶性肿瘤形成。

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

机构信息

From the Department of Surgery, VA San Diego Healthcare System and the University of California, San Diego, San Diego, CA 92161, USA.

出版信息

Pancreas. 2010 Aug;39(6):904-12. doi: 10.1097/MPA.0b013e3181ce60a3.

DOI:10.1097/MPA.0b013e3181ce60a3

PMID:20182393

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2888635/

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.

摘要

目的

我们之前的研究表明，二价阳离子可调节α2β1 整合素介导的胰腺癌细胞与 I 型胶原在二维（2D）水平上的相互作用，包括细胞黏附、迁移和增殖。目前，我们在一种新型的 3D 体外模型中研究了二价阳离子依赖性α2β1 整合素介导的胰腺癌细胞在 I 型胶原上的黏附和增殖。

方法

在 2D 和 3D 条件下，使用细胞黏附、增殖和抗体抑制实验以及显微镜和免疫印迹技术进行了这些研究。

结果

与 2D 条件一样，3D 条件下细胞在 I 型胶原上的黏附也依赖于 Mg，且被 Ca 抑制。3D 条件下的增殖也依赖于 Mg，但在促进最大细胞黏附的 Mg 浓度和低于 Mg 的 Ca 浓度存在时达到最大值。免疫印迹研究表明，在 2D 和 3D 的 I 型胶原上观察到的细胞间黏附的二价阳离子依赖性变化与 E-钙黏蛋白和β-连环蛋白表达的变化有关。抗体抑制实验进一步表明，在改变的二价阳离子条件下，α2β1 整合素特异性介导 3D 中 I 型胶原上的增殖。