Role of Immune Cells in Brain Metastasis of Lung Cancer Cells and Neuron-Tumor Cell Interaction

Abstract

Following any type of brain injury such as lesion, stroke, and tumor/cancer invasion, microglia are rapidly activated and recruited to the site of injury. Microglia is the main immune effector cell population of the central nervous system and control immune cell recruitment. However, the molecular mechanism of brain metastasis and interaction between neuron-glia-tumor cells are poorly understood. Therefore, we established an animal model for brain metastasis using human lung cancer-derived cells (HARA-B) in nude mice. Accumulation of activated microglia was observed around tumor cells depending on the size of metastatic foci and the area of the brain. In in vitro studies, conditioned medium from primary cultured mouse microglia inhibited the proliferation of tumor cells, while tumor cell-conditioned medium inhibited the proliferation of primary cultured neurons from mouse cortex. Though the responsible factors released from microglia and tumor cells are still under investigation, these studies will contribute to the understanding of the mechanism of cell-cell interaction in the brain and the possible therapeutic target for brain metastasis.