G-CSFR在非小细胞肺癌的表达及其意义

Expression of Granulocyte Colony-stimulating Factor Receptor and Its Role in Non-small Cell Lung Cancer

作者: 专业:肿瘤学 导师:束永前 年度:2009 学位:硕士  院校: 南京医科大学

Keywords

Colony-stimulating factor receptor, Non-small cell lung cancer, A549 cell line, Apoptosis

        粒细胞集落刺激因子(granulocyte colony-stimula-ting factor,G-CSF)是由单核细胞、成纤维细胞和内皮细胞等产生的一种造血生长因子,能与细胞表面的特定受体即粒细胞集落刺激因子受体相结合,促使中性粒细胞系造血祖细胞生长和分化,保护中性粒细胞避免凋亡并进而加强它们的功能。在临床上,G-CSF被广泛地用于由各种原因引起的粒细胞减少症并取得了较好的疗效。目前除了造血细胞外,已发现其他部分组织器官亦表达粒细胞集落刺激因子受体(granulocyte colony-stimulating factor receptor,G-CSFR),以及多种肿瘤细胞对G-CSF的反应性提示我们,G-CSF可能具有以前未知的功能。目的:研究G-CSFR在非小细胞肺癌中的表达,以进一步探讨G-CSF及其受体在非小细胞肺癌发生、发展过程中的作用。方法:应用免疫组化SP法分别检测60例非小细胞肺癌及15例肺良性病变患者石蜡包埋标本组织中G-CSFR的表达;PI单标流式细胞术检测肺腺癌细胞株A549上G-CSFR的表达;Brdu标记法检测重组人粒细胞集落刺激因子(recombinant human granulocyte colony-stimulating factor receptor,rhG-CSF)对肺腺癌A549细胞株的增殖影响以及Annexin V-FITC/PI法检测其是否对细胞的凋亡产生作用。结果:免疫组化表明非小细胞肺癌中有明显的G-CSFR蛋白的表达,并明显高于肺良性病变组织;统计分析结果显示,CSFR阳性表达与年龄、性别、肿瘤病理分期及有无淋巴结转移无关(P=0.520、P=0.438、P=0.179及P=0.246),而与肿瘤大小有关(P= 0.046、P<0.5)。同时A549细胞株高表达G-CSFR, rhG-CSF对A549细胞的增殖无明显影响,但可抑制其凋亡。结论:G-CSFR在非小细胞肺癌中的表达较肺良性病变组织明显上调,G-CSFR的阳性表达与肿瘤大小有关,其表达可能对肿瘤细胞的凋亡有抑制作用,进而促进肿瘤的发生、发展。
    Granulocyte colony-stimulating factor is a kind of hematopietic growth factor which is produced by monocytes, fibroblasts and endothelial cells. Granulocyte colony-stimulating factor acts on neutrophilic progenitor cells by binding to specific cell surface receptors, thereby stimulates proliferation, differentiation, commitment, and selected end-cell functional activation including enhanced phagocytic ability, priming of the cellular metabolism associated with respiratory burst, antibody dependent killing and the increased expression of some functions associated with cell surface antigens, Granulocyte colony-stimulating factor is effective and safe for treatment of neutropenia. At present, Granulocyte colony-stimulating factor receptor is not only presented in hematopoietic cells, but also in other organs. The reactive of tumor cells to granulocyte colony-stimulating factor also point out that granulocyte colony-stimulating factor may has some undiscovered functions.Objective To investigate expression of granulocyte colony-stimulating factor receptor in non-small cell lung cancer and its function in the occurrence and development of non-small cell lung cancer.Methods Granulocyte colony-stimulating factor receptor expression was evaluated by immunohistochemistry in sixty specimens of non-small cell lung cancer and fifteen of lung benign lesionss. Granulocyte colony-stimulating factor receptor in adenocarcinoma of lung cell line A549 was analyzed using flow cytometry by a propidium iodide method. The effect of recombinant human granulocyte colony-stimulating factor to the proliferation of the A549 cell line was observed by BRDU-marking method. The effect of recombinant human granulocyte colony-stimulating factor to the apoptosis of A549 cells was detected by annexin V-FITC/PI method.Results Immucohistochemical analyses revealed that granulocyte colony-stimulating factor receptor was expressed in the NSCLC and it appeared to be up-regulated compared with the lung benign lesionss. The results of the statistical analysis presentationed no relationship between the expression of granulocyte colony-stimulating factor receptor and the age,gender, tumor stage and lymphatic metastasi(sP =0.520、P=0.438、P=0.179 and P=0.246),and a correlation was found between granulocyte colony-stimulating factor receptor expression and tumor size(P=0.046). Flow cytometry showed granulocyte colony-stimulating factor receptor was high expressed in A549 cell line, recombinant human granulocyte colony-stimulating factor had no effect on the growth of the A549 cells but it inhibited its apoptosis.Conclusion Granulocyte colony-stimulating factor receptor is frequently expressed in non-small cell lung cancer and its expression is related with tumor size, thus supporting a hypothesis that granulocyte colony-stimulating factor plays a role in the inhibition of the cell apoptosis, thereby, contribute to the occurrence and development of tumor.
        

G-CSFR在非小细胞肺癌的表达及其意义

中文摘要4-6
英文摘要6-7
前言8-11
材料与方法11-18
    1.材料11-14
    2 方法14-17
    3.统计学处理17-18
结果18-20
    1.G-CSFR 在非小细胞肺癌和肺良性病变组织的 G-CSFR 的表达18
    2.G-CSFR 的检测18-19
    3. brdu 标记法检测细胞增殖19
    4.细胞早期凋亡率检测19-20
分析与讨论20-23
结论23-24
参考文献24-27
附图27-31
文献综述31-46
    参考文献42-46
附录46-49
    英文缩写及中英文全名对照46-47
    攻读学位期间发表文章情况47-48
    致谢48-49
        下载全文需10


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