Divalent cations modulate alpha2beta1 integrin-mediated malignancy in a novel 3-dimensional in vitro model of pancreatic cancer.
Divalent cations modulate alpha2beta1 integrin-mediated malignancy in a novel 3-dimensional in vitro model of pancreatic cancer.
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在胰腺癌的新型三维体外模型中，二价阳离子调节 α2β1 整合素介导的恶性肿瘤。
DOI：
10.1097/mpa.0b013e3181ce60a3
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发表时间：
2010
期刊：
影响因子：
2.9
通讯作者：
Bouvet,Michael
中科院分区：
文献类型：
--
作者：
Grzesiak,JohnJ;Vargas,Fabian;Bouvet,Michael
目的：我们以前发现，二价阳离子调节α 2 β 1整合素介导的胰腺癌细胞与I型胶原蛋白的二维（2D）相互作用，包括细胞粘附，迁移和增殖。目前，我们研究了二价阳离子依赖的α 2 β 1整合素介导的胰腺癌细胞粘附和增殖的I型胶原在一个新的三维体外模型。方法：细胞附着，增殖，和抗体抑制试验的I型胶原在二维和三维，显微镜和免疫印迹用于这些研究。3D中的增殖也是Mg 2+依赖性的，但是当Mg 2+以促进最大细胞粘附的浓度存在并且Ca 2+以低于Mg 2+的浓度存在时，增殖最大。免疫印迹研究表明，在2D和3D中在I型胶原上观察到的细胞-细胞粘附的二价阳离子依赖性变化与E-钙粘蛋白和β-连环蛋白表达的变化相关。抗体抑制试验进一步表明，α 2 β 1整合素特异性介导增殖的I型胶原蛋白在3D下改变二价阳离子conditions.Conclusions：二价阳离子移位可以激活α 2 β 1整合素介导的恶性肿瘤在富含I型胶原蛋白的3D胰腺癌肿瘤微环境。
Objectives:We previously showed that divalent cations regulate α 2 β 1 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 α 2 β 1 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 2+-dependent and inhibited by Ca 2+. Proliferation in 3D is also Mg 2+-dependent, but maximal when Mg 2+ is present at concentrations that promote maximal cell adhesion and Ca 2+ is present at concentrations less than Mg 2+. 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 β-catenin expression. Antibody inhibition assays indicate further that the α 2 β 1 integrin specifically mediates proliferation on type I collagen in 3D under altered divalent cation conditions.Conclusions:Divalent cation shifts could activate α 2 β 1 integrin-mediated malignancy in the type I collagen-rich 3D tumor microenvironment of pancreatic cancer.