糖皮质激素抑制肿瘤细胞迁移机制及在体对肿瘤进展影响的研究

项目名称： 糖皮质激素抑制肿瘤细胞迁移机制及在体对肿瘤进展影响的研究

项目编号： No.81472690

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 卢建

作者单位： 中国人民解放军第二军医大学

项目金额： 72万元

中文摘要： 应激与肿瘤的关系日益受到关注，糖皮质激素(GC)作为体内重要的应激激素， 除了具有强大的免疫抑制和抗炎作用外，还能改变肿瘤的微环境，并直接调节肿瘤细胞的增殖和凋亡。我们前期的工作表明GC还能促进肿瘤细胞粘附，导致细胞骨架重构，并能明显抑制细胞迁移。细胞迁移是决定肿瘤细胞侵袭转移的重要因素。目前GC抑制细胞迁移的机制以及在体对肿瘤进展的影响尚不清楚。本课题拟进一步研究GC抑制细胞迁移和侵袭的作用及其机制，确定介导GC作用的靶蛋白和相关信号转导通路，并通过免疫功能完整和免疫缺陷小鼠的荷瘤模型研究GC对肿瘤进展和转移的影响，明确GC在整体对肿瘤进展的综合作用及其作用的主要环节（是对免疫系统的作用，还是对肿瘤局部的作用，或是二者之和）。该研究不仅有助于阐明GC调控肿瘤细胞迁移侵袭的机制和作为重要应激激素的GC对肿瘤进展和转移的影响，还能更为全面的认识GC的作用，为临床合理使用GC提供理论依据。

中文关键词： 糖皮质激素；糖皮质激素受体；细胞迁移；肿瘤进展；肿瘤转移

英文摘要： Emerging evidence showed that chronic stress has an impact on tumor growth and progression. As an important stress hormone, glucocorticoid (GC) not only has strong immunosuppression and antiinflammatory effects, but also can affect tumor biology by changing the tumor microenviroment as well as play a direct role in regulating proliferation, invasion and apoptosis of tumor cells. Recently we found that dexamethasone (Dex), a synthetic GC significantly enhanced cell adhesion to extracellular matrix (ECM) and inhibit the migration of ovarian cancer cells and osteosarcoma cells. However it remains unclear the mechanism by which GC inhibits migration of tumor cells and whether GC directly affect the progression of tumor through the glucocorticoid receptor (GR) pathway in vivo. In this study, we will investigate：（1）the effects of GC on cell migration and invasion, as well as the mechanism by identifying GC-regulated target genes and signaling pathways involved in the effect of GC; (2) the influence of glucocorticoids on tumor progress and metastasis in vivo using mouse model with or without immunodeficiency. This study will not only help clarify the mechanism by which GC inhibit migration and invasion of tumor cells, but also determine the effect of glucocorticoids on tumor progress and metastasis in vivo.

英文关键词： Glucocorticoid;Glucocorticoid receptor;cell migration;tumor progress;tumor metastasis