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

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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.