Establishment of a highly metastatic human lung cancer cell line and investigaion of mechanism associating with the highly metastatic ability

高转移性人肺癌细胞系的建立及高转移能力相关机制的研究

• 批准号: 06670633
• 负责人: KUDOH Shoji
• 金额: $ 0.77万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670633/
• 关键词: Lung Cancer; Cell Line; Metastases; Highly metastatic cell line; Nude mouse; Adhesion; Invasion; Integrin; ヒト肺癌細胞株

<ABSTRACT>Integrins are the major receptors by which cells attach to extracellular matrix and play an important role in cancer metastasis. To investigate the relation of integrins and metastasis, we established a highly metastatic human non-small cell lung cancer (NSCLC) cell line in nude mice, designated PC9/F9, by repeated intravenous injection of parent cell (PC9). In cell adhesion assay, PC9 adhered to laminin but PC9/F9 adhered more strongly. Farther more, PC9/F9 adhered type IV collagen and fibronectin. FACS scan analysis showed expression of VLA-2, VLA-3 and VLA-6 in PC9, VLA-2, VLA-3, VLA-4, VLA-5 and VLA-6 in PC9/F9. In adhesion inhibition assay, adhesion of PC9 to laminin was inhibit by anti-human alpha3 and beta1 integrin monoclonal antibody (Mo-Ab), on the other hand, adhesion of PC9/F9 to laminin was not inhibit by anti-beta1 integrin Mo-Ab and any of anti-alpha integrin Mo-Ab. Adhesion of PC9/F9 to type IV collagen was inhibited by anti-alpha2 and anti-beta1 integrin Mo-Ab. Adhesion of PC9/F9 to fibronectin was inhibit by anti-alpha5 and anti-beta1 integrin Mo-Ab. Anti-alpha4 Mo-Ab moderately inhibit adhesion of PC9/F9 to fibronectin. These data suggest that beta1 integrins enhance the ability of human NSCLC cells to metastasize by changing their expression and function.

<tractract>整联蛋白是细胞附着在细胞外基质上并在癌症转移中起重要作用的主要受体。为了研究整联蛋白和转移的关系，我们通过重复对父母细胞的静脉注射（PC9）建立了指定为PC9/F9的裸鼠中高度转移性人类非小细胞肺癌（NSCLC）细胞系（指定为PC9/F9）。在细胞粘附测定中，PC9遵守层粘连蛋白，但PC9/F9更强烈。更远，PC9/F9粘附的IV型胶原蛋白和纤连蛋白。 FACS扫描分析表明，PC9，VLA-2，VLA-3，VLA-4，VLA-4，VLA-5和VLA-6在PC9/F9中的VLA-2，VLA-3和VLA-6的表达。在粘附抑制测定中，抗人类α3和Beta1整合素单克隆抗体（MO-AB）抑制PC9对层粘连蛋白的粘附，另一方面，抗Beta1整合蛋白mo-ab-ababpha粘附于PC9/F9对拉amin蛋白的粘附并不能抑制。 PC9/F9对IV型胶原蛋白的粘附被抗α2和抗BETA1整合素MO-AB抑制。 PC9/F9对纤连蛋白的粘附被抗α5和抗BETA1整合素MO-AB抑制。抗α4Mo-AB中度抑制PC9/F9对纤连蛋白的粘附。这些数据表明，β1整合素通过改变其表达和功能来增强人NSCLC细胞转移的能力。