Establishment of brain metastatic model of NS CLC and investigation for the mechanism of brain metastasis of NS CLC

NS CLC脑转移模型的建立及NS CLC脑转移机制的探讨

• 批准号: 12671326
• 负责人: YOSHIMASU Tatsuya
• 金额: $ 2.05万
• 依托单位: Wakayama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671326/
• 关键词: Lung Cancer; Brain Metastasis; Integrin; Laminin

The aim of this study was to clarify the roles of integrin and extracellular matrix (ECM) in the process of non-small cell lung cancer (NSCLC) brain metastasis. We established an in vivo model of brain metastasis of human NSCLC cell line EBC-1/original in athymic mice, and established highly brain metastatic subdone EBC-1/brain and highly bone metastatic subdone EBC-1/bone. Integrin expression of these subdones was evaluated by flowcytometry. In vitro cell attachment, migration and proliferation assays with ECMs were performed using these subdones. Expression of integrin alpha 3 subunit was higher in EBC-1/brain than in both EBC-1/original and EBC-1/bone. In vitro cell attachment, migration, and proliferation assays revealed that EBC-1/brain had higher affinity and higher reactivity to laminin than EBC-1/original and EBC-1/bone. Blocking of integrin a3b1 significantly (p<0.05) decreased brain metastasis by EBC-1/brain. Interaction of integrin alpha 3 beta 1 and laminin plays important roles in the process of brain metastasis of non-small cell lung cancer.

本研究旨在探讨整合素和细胞外基质在非小细胞肺癌脑转移过程中的作用。我们建立了人非小细胞肺癌细胞株EBC-1/original在裸鼠体内的脑转移模型，并建立了高脑转移亚组EBC-1/脑和高骨转移亚组EBC-1/骨。通过流式细胞术评估这些亚区的整合素表达。使用这些亚基进行体外细胞附着、迁移和增殖测定。整合素α 3亚基在EBC-1/脑中的表达高于EBC-1/原始和EBC-1/骨。体外细胞粘附、迁移和增殖试验表明，EBC-1/脑比EBC-1/原始和EBC-1/骨对层粘连蛋白具有更高的亲和力和更高的反应性。阻断整合素a3 b1显著降低EBC-1/brain的脑转移（p<0.05）。整合素α 3 β 1与层粘连蛋白的相互作用在非小细胞肺癌脑转移过程中起重要作用。