肿瘤相关巨噬细胞通过Kindlin-2基因调节胃癌细胞侵袭转移的作用机制

Resent studies show that tumor associated macrophages (TAMs) play an important role in the invasion and metastasis of cancer. However, the role of TAMs in the progression of gastric cancer remains unclear.In our previous research, we have found that TAMs promoted the invasion and metastasis of gastric cancer through Kindlin-2 gene.Whereas, the mechanism need be clarified. In this study, we intend to use 3D invasion assay, flow cytometry and adhesion assay to measure the role of Kindlin-2 in the invasion rate, proliferation, apoptosis and ahension ability of gastric cancer cells induced by TAMs under normal or hypoxic conditions; dual luciferase report system,electrophoretic mobility shift assay and site-directed mutagenesis were used to study the the mechanism of TGFβ2、IL8 secreted by TAMs regualting the Kindlin-2 expression through its transcription factor NFк-B ; use immunohistochemical techniques to study the relationship between infiltration of TAMs in human gastric cancer tissues and clinical pathological parameters, prognosis and the expression of Kindlin-2 protein; use gastric carcinoma oncogeneis model and metastasis assay in nude mice to verify the mechanism of Kindlin-2 affecting the the invasion and metastasis of gastric cancer induced by TAMs in vivo. This study will elucidate the role and mechanism o TAMs affecting the invasion and metastasis through Kindlin-2 gene, which might provide the basis for possible new treatment options and ideas.

近年认为，肿瘤相关巨噬细胞（TAMs）在肿瘤侵袭转移中发挥重要作用，但TAMs在胃癌中的研究较少。我们前期发现：TAMs可通过新型黏着斑基因Kindlin-2促进胃癌侵袭转移，但机制尚不明确。本课题拟用3D肿瘤细胞侵袭实验、流式细胞术等方法探索Kindlin-2在TAMs调节胃癌细胞侵袭、增殖、凋亡和粘附中的作用；用双荧光素酶实验、凝胶迁移电泳试验、基因定点突变等方法研究TAMs通过分泌细胞因子（TGFβ2、IL8）经转录因子NFк-B 作用于Kindlin-2调节胃癌侵袭转移的分子机制；用免疫组化等方法在人胃癌组织探讨TAMs浸润与Kindlin-2表达、临床病理指标、预后的相关性；用裸鼠成瘤实验等在动物体内进一步验证TAMs通过Kindlin-2影响胃癌侵袭转移的机制。望该研究能初步阐明TAMs通过黏着斑基因Kindlin-2在调节胃癌侵袭转移的分子机制，为胃癌治疗提供新靶点和新思路。

近年认为，肿瘤相关巨噬细胞（ TAMs）在肿瘤侵袭转移中发挥重要作用，但 TAMs.在胃癌中的研究较少。我们前期发现： TAMs 可通过新型黏着斑基因 Kindlin-2 促进胃癌侵袭.转移，但机制尚不明确。本课题拟用 3D 肿瘤细胞侵袭实验、流式细胞术等方法探索 Kindlin-.2 在 TAMs 调节胃癌细胞侵袭、增殖、凋亡和粘附中的作用；用双荧光素酶实验、 凝胶迁移电.泳试验、基因定点突变等方法研究 TAMs 通过分泌细胞因子（ TGFβ2、 IL8）经转录因子 NFк.-B 作用于 Kindlin-2 调节胃癌侵袭转移的分子机制；用免疫组化等方法在人胃癌组织探讨.TAMs 浸润与 Kindlin-2 表达、临床病理指标、预后的相关性；用裸鼠成瘤实验等在动物体内.进一步验证 TAMs 通过 Kindlin-2 影响胃癌侵袭转移的机制。望该研究能初步阐明 TAMs 通过.黏着斑基因 Kindlin-2 在调节胃癌侵袭转移的分子机制，为胃癌治疗提供新靶点和新思路。