本文選題：腎細(xì)胞癌 + 內(nèi)皮祖細(xì)胞��； 參考：《南京醫(yī)科大學(xué)》2014年碩士論文

【摘要】：背景：在內(nèi)皮細(xì)胞基礎(chǔ)上形成毛細(xì)血管的血管新生已不再是腫瘤新生血管的唯一方式,通過(guò)動(dòng)員內(nèi)皮祖細(xì)胞(EPCs)形成新血管同樣為腫瘤新生血管化的重要途徑。新生血管化在腫瘤的進(jìn)展、轉(zhuǎn)移和復(fù)發(fā)中具有重要作用。惡性腫瘤微環(huán)境下的多種因素可動(dòng)員骨髓中的EPCs入外周血,最終募集到腫瘤局部組織的血管床,參與腫瘤新生血管的形成,并對(duì)腫瘤的生物學(xué)特性產(chǎn)生重要影響。到目前為止,尚無(wú)有關(guān)EPCs對(duì)腎癌新生血管過(guò)程產(chǎn)生影響的報(bào)道。本研究通過(guò)建立裸鼠腎癌動(dòng)物模型,檢測(cè)腎癌進(jìn)展中EPCs的分布特征,探索EPCs的動(dòng)員特征以及在腎癌新生血管化中的作用 目的：檢測(cè)EPCs在腎癌(RCC)進(jìn)展中的分布特征,探討EPCs的動(dòng)員機(jī)制以及在腫瘤新生血管化中的作用。 方法：雄性BALB/c裸鼠隨機(jī)分為3組：RCC組,Sham組,Normal組。分別在RCC組小鼠右腎下極移植人腎癌細(xì)胞ACHN后于21,28,35,42,49天分別處死各時(shí)間段的相應(yīng)數(shù)量的三組小鼠,并收集相關(guān)標(biāo)本,測(cè)量RCC組腫瘤直徑,評(píng)估循環(huán)內(nèi)皮祖細(xì)胞(CEPCs),血漿血管內(nèi)皮生長(zhǎng)因子(VEGF)及基質(zhì)細(xì)胞衍生因子(SDF-1)水平。并檢測(cè)正常腎組織(NT),假手術(shù)腎組織(ST),癌旁組織(AT),癌組織(TT)中EPCs水平及分布情況,微血管密度(MVD)、VEGF、SDF-1、內(nèi)皮生長(zhǎng)因子受體2(FLK)、趨化因子受體(CXCR4)等mRNA表達(dá)。 結(jié)果：與Normal以及Sham組比較,RCC組CEPCs和血漿VEGF、SDF-1表達(dá)水平明顯升高(P0.05), CEPCs和血VEGF、SDF-1之間存在正相關(guān)(rl=0.584,r2=0.579)。AT中VEGF和SDF-1表達(dá)顯著高于TT及NT(P0.05),且與血漿VEGF、SDF-1呈正相關(guān)(rl=0.618,r2=0.421)。AT中EPCs水平在28天后逐漸升高,明顯高于TT和NT中的表達(dá)(P0.05),且與CEPCs之間呈正相關(guān)(r=0.857)；TT中EPCs水平則先升高后逐漸降低,且明顯高于NT中表達(dá)(P0.05),和CEPCs之間則無(wú)關(guān)聯(lián)。免疫熒光檢測(cè)EPCs主要聚集于AT；免疫組化檢測(cè)AT中MVD明顯高于TT和NT,而TT中MVD則低于NT(P0.05)。 結(jié)論:癌旁組織中的血管生長(zhǎng)因子VEGF和SDF-1在EPCs動(dòng)員過(guò)程中具有重要作用。EPCs可通過(guò)分泌促血管生長(zhǎng)因子,增加新生血管形成共同促進(jìn)腫瘤新生血管化,進(jìn)而促進(jìn)腎癌的進(jìn)展。
[Abstract]:Background: capillary angiogenesis based on endothelial cells is no longer the only way of tumor angiogenesis. The mobilization of endothelial progenitor cells (EPCs) to form new blood vessels is also an important way of tumor angiogenesis. Neovascularization plays an important role in tumor progression, metastasis and recurrence. Many factors in the microenvironment of malignant tumor can mobilize EPCs from bone marrow into peripheral blood and eventually recruit the vascular bed of tumor local tissue to participate in the formation of tumor neovascularization and play an important role in the biological characteristics of tumor. Up to now, there are no reports about the effect of EPCs on the angiogenesis of renal cell carcinoma. In this study, an animal model of renal cell carcinoma in nude mice was established to detect the distribution of EPCs in the progression of renal cell carcinoma, and to explore the characteristics of EPCs mobilization and its role in the angiogenesis of renal cell carcinoma. Objective: to investigate the distribution of EPCs in the progression of renal cell carcinoma (RCC). To explore the mobilization mechanism of EPCs and its role in tumor neovascularization. Methods: male BALB _ (r-c) nude mice were randomly divided into three groups. Human renal cancer cells (ACHN) were transplanted into the right inferior renal pole of RCC group. The corresponding number of RCC mice were killed on day 21, 2835, 4249, respectively. The tumor diameter of RCC group was measured. The levels of circulating endothelial progenitor cells (CEPCs), plasma vascular endothelial growth factor (VEGF) and stromal cell derived factor (SDF-1) were evaluated. The levels and distribution of EPCs in normal renal tissues (NT), sham operated renal tissues (St), paracancerous tissues (AT), cancer tissues (TT), microvessel density (MVD) VEGFF- SDF-1, endothelial growth factor receptor 2 (FLK) and chemokine receptor (CXCR4) were detected. Results: compared with normal and Sham groups, the expression of VEGF and SDF-1 in plasma and CEPCs in RCC group was significantly higher than that in normal group (P0.05). There was a positive correlation between CEPCs and serum VEGFF-1 SDF-1 (rlln0.584r2tir 0.579). The expression of VEGF and SDF-1 in RCC group was significantly higher than that in TT group and NT group (P0.05), and there was a positive correlation between VEGF and SDF-1 expression in plasma VEGFFff-1 (rllO0.618mr20.421). The level of EPCs in AT increased gradually after 28 days, and the expression of SDF-1 in RCC group was significantly higher than that in TT and NT group (P0.05). The expression of EPCs in TT and NT was significantly higher than that in TT and NT (P0.05), and there was a positive correlation between EPCs and CEPCs (r-0.857). The level of EPCs in TT increased at first and then decreased gradually, and was significantly higher than that in NT (P0.05), and there was no correlation between EPCs and CEPCs. The MVD in AT was significantly higher than that in TT and NTand the MVD in TT was lower than that in NT (P0.05). Conclusion: VEGF and SDF-1 in paracancerous tissues play an important role in the mobilization of EPCs. EPCs can promote tumor angiogenesis by secreting angiogenic factors and promote the progression of renal cell carcinoma.
【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R737.11

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 ;The recruitment of exogenous endothelial progenitor cells in lung tumor model of nude mice[J];癌癥;2010年11期

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本文編號(hào)：2066189