Grzesiak John J, Bouvet Michael
Department of Surgery, University of California San Diego, San Diego, CA, USA.
Pancreas. 2007 Mar;34(2):220-8. doi: 10.1097/01.mpa.0000250129.64650.f6.
Pancreatic cancer cells express 2 known collagen-binding integrins, alpha2beta1 and alpha1beta1. The ligand-binding specificity of alpha1beta1 and the integrin/s responsible for mediating the malignant phenotype on type I collagen in the 3-dimensional (3D) tumor microenvironment have not been determined in pancreatic cancer. The aim of the present study was to determine the ligand-binding specificities of the alpha2beta1 and alpha1beta1 integrins using a novel 3D in vitro model of pancreatic cancer.
We used 3D type I collagen-glycosaminoglycan scaffolds in adhesion and proliferation assays with pancreatic cancer cell lines, as well as affinity chromatography and inhibition of adhesion assays.
We demonstrate for the first time that CFPAC, BxPC-3, Colo-357, FG, and Panc-1 cells attach to 3D type I collagen scaffolds in an alpha2beta1-specific manner and that this integrin-specific adhesion is required for subsequent cell proliferation. MiaPaCa-2 cells, which do not express the alpha2beta1 or alpha1beta1 integrins, do not attach or proliferate on 3D type I collagen scaffolds. We also demonstrate the novel finding that the alpha1beta1 integrin is a type IV collagen receptor in pancreatic cancer cells.
These data indicate that targeting alpha2beta1 integrin-specific type I collagen adhesion may have therapeutic value in the treatment of pancreatic cancer.
胰腺癌细胞表达两种已知的胶原结合整合素，α2β1和α1β1。在胰腺癌中，尚未确定α1β1的配体结合特异性以及在三维（3D）肿瘤微环境中介导I型胶原上恶性表型的整合素。本研究的目的是使用一种新型的胰腺癌3D体外模型来确定α2β1和α1β1整合素的配体结合特异性。
我们在胰腺癌细胞系的黏附与增殖试验中使用了3D I型胶原-糖胺聚糖支架，以及亲和层析和黏附抑制试验。
我们首次证明，CFPAC、BxPC-3、Colo-357、FG和Panc-1细胞以α2β1特异性方式附着于3D I型胶原支架，并且这种整合素特异性黏附是随后细胞增殖所必需的。不表达α2β1或α1β1整合素的MiaPaCa-2细胞在3D I型胶原支架上不附着或增殖。我们还证明了一个新发现，即α1β1整合素是胰腺癌细胞中的IV型胶原受体。
这些数据表明，靶向α2β1整合素特异性的I型胶原黏附可能在胰腺癌治疗中具有治疗价值。
