신경교종의 성장과 미세환경 형성에 있어 미세아교세포의 저산소 유도 전사인자 역할에 관한 연구

Abstract

Glioma is the most common and malignant central nervous system tumor. Despite its lethality and prevalence, it is hard to be cured by traditional therapies such as surgery, chemotherapy, and radiotherapy. Tumor microenvironment receives much attention as a new target for therapy – for example, tumor hypoxia, a tumor microenvironmental factor is a major factor contributing to therapy resistance. Therefore, in this thesis we examined glioma microenvironment and the effect of hypoxia-inducible factor 1α (HIF-1α) in microglia modulating glioma growth and tumor microenvironment. To do this, we used myeloid specific Hif-1α knock out mice generated in this laboratory by crossing hS100A8-Cre mice with Hif-1α floxed mice. In gliomas grown in mice deficient for Hif-1α in microglia, we observed that the number of tumor vessels, infiltrated microglia/macrophages, and the extent of tumor hypoxia were significantly increased compared to those in wild-type mice, although the tumor growth was similar. All these results suggested that modulation of only one gene in one type of immune cell population, namely Hif-1α gene in microglia could modulate tumor microenvironment, which may further modulate tumor response to anticancer therapy, such as radiotherapy.