趋化因子受体CXCR7在乳腺癌中的表达及其临床意义

发布时间：2017-12-27 19:24

本文关键词：趋化因子受体CXCR7在乳腺癌中的表达及其临床意义　出处：《山东大学》2016年硕士论文　论文类型：学位论文

更多相关文章： 乳腺癌 CXCR7 趋化因子 肿瘤转移

【摘要】：研究背景和目的：近年来,我国女性的乳腺癌发病率呈逐年上升的趋势。了解乳腺癌的分子生物学特性,阐明其发病机制,对于最终治愈乳腺癌有着重要的意义。已有证据表明,趋化因子及其受体在肿瘤的生长、浸润及转移等一系列复杂的生物学过程中发挥一定的作用。因此,研究趋化因子及其受体在乳腺癌中的作用,对进一步阐明乳腺癌生长及转移的分子机制有一定的意义。目前趋化因子受体CXCR7在乳腺癌中的作用还不十分清楚。本研究的目的是研究趋化因子受体CXCR7在乳腺癌细胞系及人类标本中的表达情况,并对其表达在乳腺癌中的意义作初步探索。方法：首先采用Flow cytometry 及 Western blot检测CXCR7在不同的人类乳腺癌细胞系的表达水平。采用慢病毒包系统包装并获得CXCR7过表达慢病毒,感染MDA-MB-231细胞系,上调MDA-MB-231细胞CXCR7的表达。然后,我们在体外实验中利用Flow cytometry、CCK-8等方法来检测CXCR7基因过表达前后乳腺癌细胞的增殖能力以及细胞周期分布的变化。我们还对人类乳腺癌组织标本的CXCR7的表达情况作了相应研究。连续收集了山东大学附属省立医院乳腺甲状腺外科2008年2月-2009年2月间的183例乳腺癌患者的组织标本,均为浸润性乳腺癌。采用免疫组化检测分析了CXCR7在人类乳腺癌的表达情况。并且,我们比较CXCR7阴性组与CXCR7阳性组患者平均年龄、肿瘤大小、组织学分级、腋窝淋巴结状态、ER状态、PR状态、HER2状态以及复发转移发生率的差别。结果：在不同的人类乳腺癌细胞系中,CXCR7的表达水平存在一定的差异；肺高转移潜能的MDA-MB-231 HM细胞CXCR7的表达水平显著高于MDA-MB-231细胞。体外实验结果显示：CXCR7基因上调后,细胞的周期分布没有改变。而MDA-MB-231/CXCR7细胞的增殖速度明显快于MDA-MB-231及对照。人乳腺癌组织中的研究结果显示,在183例原发浸润性乳腺癌患者中,有67例患者为CXCR7阳性,阳性率为36.6%。与CXCR7阴性患者组相比较,CXCR7阳性组患者的HER2阳性率高(45.5%vs21.7%),淋巴结转移率(43.1% vs 68.7%)、肺转移发生率均较高(5.2% vs 13.4%)(P0.05)。而两组之间的年龄、肿瘤大小、核分级、ER状态、PR状态、肿瘤局部复发率及骨转移发生率等无显著差异(P0.05)结论：CXCR7在不同的人类乳腺癌细胞系中有不同水平的表达；CXCR7的表达可以促进乳腺癌细胞增殖而对细胞周期分布没有影响；CXCR7阳性患者HER2阳性率高且更容易发生淋巴结转移率及肺转移。
[Abstract]:Research background and purpose: in recent years, the incidence of female breast cancer in China is increasing year by year. Understanding the molecular biological characteristics of breast cancer and elucidating its pathogenesis are of great significance for the final cure of breast cancer. There has been evidence that chemokine and its receptors play a role in a series of complex biological processes, such as tumor growth, infiltration and metastasis. Therefore, the study of the role of chemokine and its receptor in breast cancer is of certain significance to further elucidate the molecular mechanism of breast cancer growth and metastasis. At present, the role of chemokine receptor CXCR7 in breast cancer is not very clear. The purpose of this study is to investigate the expression of chemokine receptor CXCR7 in breast cancer cell lines and human specimens, and to explore its significance in breast cancer. Methods: first, Flow cytometry and Western blot were used to detect the expression level of CXCR7 in different human breast cancer cell lines. The lentivirus package was packaged and CXCR7 overexpressed lentivirus, and the MDA-MB-231 cell line was infected, and the expression of CXCR7 in MDA-MB-231 cells was up-regulated. Then we used Flow cytometry and CCK-8 to detect the proliferation and cell cycle distribution of breast cancer cells before and after CXCR7 gene expression in vitro. We have also studied the expression of CXCR7 in human breast cancer tissue. A total of 183 breast cancer patients in breast cancer Department of Shandong University Affiliated Hospital from February 2008 to February -2009 were collected consecutively. All of them were invasive breast cancer. Immunohistochemical detection was used to analyze the expression of CXCR7 in human breast cancer. In addition, we compared the average age, tumor size, histological grade, axillary lymph node status, ER status, PR status, HER2 status and recurrence and metastasis rate between CXCR7 negative group and CXCR7 positive group. Results: in different human breast cancer cell lines, there was a certain difference in the expression level of CXCR7. The expression level of CXCR7 in MDA-MB-231 HM cells with high lung metastatic potential was significantly higher than that in MDA-MB-231 cells. The results of in vitro experiment showed that the cell cycle distribution did not change after the CXCR7 gene was up-regulated. The proliferation rate of MDA-MB-231/CXCR7 cells was significantly faster than that of MDA-MB-231 and control. In the study of human breast cancer, 67 of the 183 patients with primary invasive breast cancer were CXCR7 positive, with a positive rate of 36.6%. Compared with the CXCR7 negative group, the positive rate of HER2 in CXCR7 positive group was high (45.5%vs21.7%), the lymph node metastasis rate (43.1% vs 68.7%) and the incidence of lung metastasis were all higher (5.2% vs 13.4%) (P0.05). But there is no significant difference between the two groups in age, tumor size, nuclear grade, ER status, PR status, tumor recurrence rate and the incidence of bone metastasis (P0.05). Conclusion: CXCR7 has different expression level in human breast cancer cell lines with different CXCR7 expression; it can promote the proliferation of breast cancer cells without effect on cell cycle distribution; the positive rate of CXCR7 in HER2 positive patients was higher and more prone to lymph node metastasis and lung metastasis.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R737.9

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