肿瘤分泌的CXC家族趋化因子招募粒样髓源抑制细胞（G-MDSC）至肿瘤原发灶的作用研究
发布时间：2018-12-17 12:24
【摘要】：在肿瘤组织中,肿瘤细胞及其间质细胞分泌的细胞因子能够促进多种白细胞浸润到肿瘤原发灶中,肿瘤的生长和转移是一个极为复杂的过程,多数肿瘤具有炎症的背景,而且慢性炎症的长期刺激会增加罹患癌症的风险。本文主要研究肿瘤分泌的因子中CXC家族趋化因子,对招募粒样髓源抑制细胞(G-MDSC)至肿瘤原发灶的作用。MDSC是由骨髓中造血干细胞异常分化产生的具有免疫抑制功能的一群异质性细胞,包括2个亚群:G-MDSC和Mo-MDSC。其中G-MDSC在浸润到肿瘤里的白细胞中占20%以上,而且相比于Mo-MDSC,G-MDSC的比例会随着肿瘤的病理性演进而明显升高。我们通过构建小鼠黑色素瘤模型,以荷瘤鼠在不同荷瘤时间下的原发瘤作为实验材料,运用PCR,Transwell,细胞培养相关实验以及流式细胞术,首先探讨CXC家族趋化因子对G-MDSC迁移的影响,以及黑色素瘤细胞相对于非肿瘤细胞中CXC家族趋化因子的表达情况;然后明确皮下荷瘤不同时间对原发瘤中G-MDSC募集以及CXC家族趋化因子表达的影响;最后研究不同CXC家族趋化因子对G-MDSC的募集情况。通过以上实验发现黑色素瘤细胞中高表达CXCL1、CXCL2和CXCL5,这三种CXC家族趋化因子能够影响G-MDSC的迁移,向荷瘤小鼠原发瘤内注射相应的干涉病毒后,相比于同时期的对照荷瘤小鼠,其原发瘤组织内G-MDSC的比例显著降低,肿瘤生长速度也有所减缓。如今,人们已经逐步认识到MDSC在肿瘤发生发展过程中的重要角色,然而在原发瘤或预转移阶段肿瘤分泌因子与MDSC的相互作用机制,以及原发瘤中MDSC的比例是否会影响肿瘤生长等问题还不是很清楚。我们的研究希望能够为以肿瘤分泌因子为靶点,治疗肿瘤等各类炎性疾病等提供线索。
[Abstract]:In tumor tissues, cytokines secreted by tumor cells and their interstitial cells can promote the infiltration of many kinds of leukocytes into the primary tumor. The growth and metastasis of tumor is a very complicated process, and most tumors have the background of inflammation. And long-term stimulation of chronic inflammation increases the risk of cancer. In this paper, we studied the chemokines of CXC family in tumor-secreting factors. The role of MDSC in recruiting granulocyte derived suppressor cells (G-MDSC) to primary tumor foci. MDSC is a heterogeneous group of immunosuppressive cells derived from abnormal differentiation of hematopoietic stem cells in bone marrow, including two subgroups: G-MDSC and Mo-MDSC. G-MDSC accounts for more than 20% of the leukocytes infiltrated into the tumor, and the proportion of Mo-MDSC,G-MDSC increases significantly with the pathological progression of the tumor. We constructed a mouse melanoma model and used the primary tumor of the tumor-bearing mice at different time as experimental materials, using PCR,Transwell, cell culture related experiments and flow cytometry. Firstly, the effect of CXC family chemokines on G-MDSC migration and the expression of CXC family chemokines in melanoma cells compared with non-tumor cells were investigated. Then the effects of subcutaneous tumor on G-MDSC recruitment and the expression of CXC family chemokines in primary tumors were determined. Finally, the recruitment of different CXC family chemokines to G-MDSC was studied. It was found that the overexpression of CXC family chemokines CXCL1,CXCL2 and CXCL5, in melanoma cells could affect the migration of G-MDSC, and the corresponding interference virus was injected into the primary tumor of tumor-bearing mice. Compared with the control mice, the proportion of G-MDSC in the primary tumor tissue was significantly decreased, and the tumor growth rate was also slowed down. Nowadays, people have gradually realized that MDSC plays an important role in the process of tumorigenesis and development. However, the interaction mechanism between tumor secretory factors and MDSC in primary tumor or premetastasis stage, It is not clear whether the proportion of MDSC in primary tumors affects tumor growth. Our research aims to provide clues for the treatment of various inflammatory diseases, such as tumours, with tumor secretory factors as the target.
【学位授予单位】：东北师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R73-3
本文编号：2384193
[Abstract]:In tumor tissues, cytokines secreted by tumor cells and their interstitial cells can promote the infiltration of many kinds of leukocytes into the primary tumor. The growth and metastasis of tumor is a very complicated process, and most tumors have the background of inflammation. And long-term stimulation of chronic inflammation increases the risk of cancer. In this paper, we studied the chemokines of CXC family in tumor-secreting factors. The role of MDSC in recruiting granulocyte derived suppressor cells (G-MDSC) to primary tumor foci. MDSC is a heterogeneous group of immunosuppressive cells derived from abnormal differentiation of hematopoietic stem cells in bone marrow, including two subgroups: G-MDSC and Mo-MDSC. G-MDSC accounts for more than 20% of the leukocytes infiltrated into the tumor, and the proportion of Mo-MDSC,G-MDSC increases significantly with the pathological progression of the tumor. We constructed a mouse melanoma model and used the primary tumor of the tumor-bearing mice at different time as experimental materials, using PCR,Transwell, cell culture related experiments and flow cytometry. Firstly, the effect of CXC family chemokines on G-MDSC migration and the expression of CXC family chemokines in melanoma cells compared with non-tumor cells were investigated. Then the effects of subcutaneous tumor on G-MDSC recruitment and the expression of CXC family chemokines in primary tumors were determined. Finally, the recruitment of different CXC family chemokines to G-MDSC was studied. It was found that the overexpression of CXC family chemokines CXCL1,CXCL2 and CXCL5, in melanoma cells could affect the migration of G-MDSC, and the corresponding interference virus was injected into the primary tumor of tumor-bearing mice. Compared with the control mice, the proportion of G-MDSC in the primary tumor tissue was significantly decreased, and the tumor growth rate was also slowed down. Nowadays, people have gradually realized that MDSC plays an important role in the process of tumorigenesis and development. However, the interaction mechanism between tumor secretory factors and MDSC in primary tumor or premetastasis stage, It is not clear whether the proportion of MDSC in primary tumors affects tumor growth. Our research aims to provide clues for the treatment of various inflammatory diseases, such as tumours, with tumor secretory factors as the target.
【学位授予单位】：东北师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R73-3
【参考文献】
相关期刊论文 前1条
1 ;Contribution of myeloid-derived suppressor cells to tumor-induced immune suppression,angiogenesis,invasion and metastasis[J];遗传学报;2010年07期
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