【摘要】：在腫瘤組織中,腫瘤細(xì)胞及其間質(zhì)細(xì)胞分泌的細(xì)胞因子能夠促進(jìn)多種白細(xì)胞浸潤到腫瘤原發(fā)灶中,腫瘤的生長和轉(zhuǎn)移是一個(gè)極為復(fù)雜的過程,多數(shù)腫瘤具有炎癥的背景,而且慢性炎癥的長期刺激會增加罹患癌癥的風(fēng)險(xiǎn)。本文主要研究腫瘤分泌的因子中CXC家族趨化因子,對招募粒樣髓源抑制細(xì)胞(G-MDSC)至腫瘤原發(fā)灶的作用。MDSC是由骨髓中造血干細(xì)胞異常分化產(chǎn)生的具有免疫抑制功能的一群異質(zhì)性細(xì)胞,包括2個(gè)亞群:G-MDSC和Mo-MDSC。其中G-MDSC在浸潤到腫瘤里的白細(xì)胞中占20%以上,而且相比于Mo-MDSC,G-MDSC的比例會隨著腫瘤的病理性演進(jìn)而明顯升高。我們通過構(gòu)建小鼠黑色素瘤模型,以荷瘤鼠在不同荷瘤時(shí)間下的原發(fā)瘤作為實(shí)驗(yàn)材料,運(yùn)用PCR,Transwell,細(xì)胞培養(yǎng)相關(guān)實(shí)驗(yàn)以及流式細(xì)胞術(shù),首先探討CXC家族趨化因子對G-MDSC遷移的影響,以及黑色素瘤細(xì)胞相對于非腫瘤細(xì)胞中CXC家族趨化因子的表達(dá)情況;然后明確皮下荷瘤不同時(shí)間對原發(fā)瘤中G-MDSC募集以及CXC家族趨化因子表達(dá)的影響;最后研究不同CXC家族趨化因子對G-MDSC的募集情況。通過以上實(shí)驗(yàn)發(fā)現(xiàn)黑色素瘤細(xì)胞中高表達(dá)CXCL1、CXCL2和CXCL5,這三種CXC家族趨化因子能夠影響G-MDSC的遷移,向荷瘤小鼠原發(fā)瘤內(nèi)注射相應(yīng)的干涉病毒后,相比于同時(shí)期的對照荷瘤小鼠,其原發(fā)瘤組織內(nèi)G-MDSC的比例顯著降低,腫瘤生長速度也有所減緩。如今,人們已經(jīng)逐步認(rèn)識到MDSC在腫瘤發(fā)生發(fā)展過程中的重要角色,然而在原發(fā)瘤或預(yù)轉(zhuǎn)移階段腫瘤分泌因子與MDSC的相互作用機(jī)制,以及原發(fā)瘤中MDSC的比例是否會影響腫瘤生長等問題還不是很清楚。我們的研究希望能夠?yàn)橐阅[瘤分泌因子為靶點(diǎn),治療腫瘤等各類炎性疾病等提供線索。
[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.
【學(xué)位授予單位】：東北師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R73-3

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相關(guān)期刊論文 前1條

1 ;Contribution of myeloid-derived suppressor cells to tumor-induced immune suppression,angiogenesis,invasion and metastasis[J];遺傳學(xué)報(bào);2010年07期

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本文編號：2384193