肾癌微环境介导的内皮祖细胞在肿瘤新生血管化过程中的作用及意义

发布时间：2018-06-25 13:50

  本文选题：肾细胞癌 + 内皮祖细胞　； 参考：《南京医科大学》2014年硕士论文

【摘要】：背景：在内皮细胞基础上形成毛细血管的血管新生已不再是肿瘤新生血管的唯一方式,通过动员内皮祖细胞(EPCs)形成新血管同样为肿瘤新生血管化的重要途径。新生血管化在肿瘤的进展、转移和复发中具有重要作用。恶性肿瘤微环境下的多种因素可动员骨髓中的EPCs入外周血,最终募集到肿瘤局部组织的血管床,参与肿瘤新生血管的形成,并对肿瘤的生物学特性产生重要影响。到目前为止,尚无有关EPCs对肾癌新生血管过程产生影响的报道。本研究通过建立裸鼠肾癌动物模型,检测肾癌进展中EPCs的分布特征,探索EPCs的动员特征以及在肾癌新生血管化中的作用 目的：检测EPCs在肾癌(RCC)进展中的分布特征,探讨EPCs的动员机制以及在肿瘤新生血管化中的作用。 方法：雄性BALB/c裸鼠随机分为3组：RCC组,Sham组,Normal组。分别在RCC组小鼠右肾下极移植人肾癌细胞ACHN后于21,28,35,42,49天分别处死各时间段的相应数量的三组小鼠,并收集相关标本,测量RCC组肿瘤直径,评估循环内皮祖细胞(CEPCs),血浆血管内皮生长因子(VEGF)及基质细胞衍生因子(SDF-1)水平。并检测正常肾组织(NT),假手术肾组织(ST),癌旁组织(AT),癌组织(TT)中EPCs水平及分布情况,微血管密度(MVD)、VEGF、SDF-1、内皮生长因子受体2(FLK)、趋化因子受体(CXCR4)等mRNA表达。 结果：与Normal以及Sham组比较,RCC组CEPCs和血浆VEGF、SDF-1表达水平明显升高(P0.05), CEPCs和血VEGF、SDF-1之间存在正相关(rl=0.584,r2=0.579)。AT中VEGF和SDF-1表达显著高于TT及NT(P0.05),且与血浆VEGF、SDF-1呈正相关(rl=0.618,r2=0.421)。AT中EPCs水平在28天后逐渐升高,明显高于TT和NT中的表达(P0.05),且与CEPCs之间呈正相关(r=0.857)；TT中EPCs水平则先升高后逐渐降低,且明显高于NT中表达(P0.05),和CEPCs之间则无关联。免疫荧光检测EPCs主要聚集于AT；免疫组化检测AT中MVD明显高于TT和NT,而TT中MVD则低于NT(P0.05)。 结论:癌旁组织中的血管生长因子VEGF和SDF-1在EPCs动员过程中具有重要作用。EPCs可通过分泌促血管生长因子,增加新生血管形成共同促进肿瘤新生血管化,进而促进肾癌的进展。
[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.
【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.11

【参考文献】

相关期刊论文 前1条

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

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