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

本研究的目的是阐明整合素和细胞外基质（ECM）在非小细胞肺癌（NSCLC）脑转移过程中的作用。我们在无胸腺小鼠体内建立了人非小细胞肺癌细胞系EBC-1/origin的脑转移体内模型，并建立了高脑转移亚群EBC-1/brain和高骨转移亚群EBC-1/bone。通过流式细胞术评估这些亚组的整合素表达。使用这些亚组进行体外细胞附着、迁移和细胞增殖分析。整合素α3亚基的表达在EBC-1/脑中高于EBC-1/原始和EBC-1/骨中。体外细胞附着、迁移和增殖测定表明，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 a3b1 可显着 (p<0.05) 减少 EBC-1/brain 的脑转移。整合素α3β1与层粘连蛋白的相互作用在非小细胞肺癌脑转移过程中发挥重要作用。

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.