[1]潘珍珍,姚敏敏,陈莺歌,等.乳腺癌患者的粒系分化异常现象和TGF-β1 的矛盾转换调节作用[J].南方医科大学学报,2018,(07):856.
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乳腺癌患者的粒系分化异常现象和TGF-β1 的矛盾转换调节作用()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2018年07期
页码:
856
栏目:
出版日期:
2018-06-30

文章信息/Info

Title:
Abnormal granulocyte differentiation and the paradoxical switch of transforming growth factor-β1 in breast cancer patients
作者:
潘珍珍姚敏敏陈莺歌邓九零颜美秋高建莉
关键词:
乳腺癌造血干细胞粒系分化转化生长因子矛盾转换
Keywords:
breast cancer hematopoietic stem cells granulocytic differentiation transforming growth factor- β1 paradoxical switch
摘要:
目的探讨乳腺癌患者外周血粒系分化异常的主要特点,并体外验证以转化生长因子(TGF-β1)为代表的肿瘤相关因子与 造血干细胞(HSC)粒系分化和乳腺癌血象的关系。方法回顾性对比分析52例乳腺癌患者与47例正常人的外周血粒系血象的 特点。通过小鼠脾脏HSC体外集落形成实验、流式细胞仪技术,分析TGF-β1对集落形成情况和Gr-1+CD11b+粒系细胞比例的 影响,以验证肿瘤关键因子TGF-β1在HSC粒系分化中的作用及与肿瘤血象异常的关系。结果乳腺癌患者白细胞计数、中性 粒细胞计数、粒细胞总数、粒细胞占白细胞比例、中性粒-淋巴细胞比率明显升高(P<0.05),而嗜酸性粒细胞计数及分类显著降 低(P<0.05)。集落形成实验表明荷瘤小鼠脾细胞的粒细胞-单核细胞集落生成单位、红细胞爆裂型集落生成单位、单核-巨噬细 胞集落生成单位显著多于正常小鼠(P<0.05)。加入TGF-β1后荷瘤小鼠脾脏HSC的粒系分化能力受促进。结论乳腺癌患者 存在明显的粒系分化异常,可能与癌组织分泌的TGF-β1等各类生长因子诱导HSC分化失衡有关。TGF-β1对脾脏HSC克隆、 粒系分化的调节存在矛盾转换现象。
Abstract:
Objective To analyze the characteristics of abnormal granulocytic differentiation in breast cancer patients and explore the role of TGF-β1 in granulocytic differentiation of hematopoietic stem cells (HSCs) and tumor development. Methods Blood samples were collected from 52 patients with invasive ductal carcinoma and 47 healthy donors. The distribution of granulocytes was compared between the two groups and the effects of surgery and radiotherapy on granulocytes were analyzed. The relationship between granulocyte abnormalities and the clinicopathological characteristics of the patients was analyzed. Spleen hematopoietic stem cells isolated from normal and tumor-bearing mice were cultured and treated with TGF-β1, and colony formation of the myeloid cells was compared and the proportion of granulocytes was analyzed with flow cytometry. Results The white blood cell (WBC) count, neutrophils, total granulocytes, granulocyte ratio in the total WBCs, and neutrophil/lymphocyte ratio (NLR) were significantly increased (P<0.05), while the eosinophils and its subpopulations were obviously decreased (P<0.05) in breast cancer patients. Clone formation experiments showed that the numbers of CFU-GM, BFU-E and CFU-M colonies were significantly greater in the spleen cells from tumor-bearing mice than in those from normal mice (P<0.05). TGF- β1 treatment obviously suppressed clone formation in spleen HSCs from normal mice but significantly promoted the proliferation and granulocyte differentiation of the spleen HSCs from tumor-bearing mice. Conclusion Breast cancer patients have obvious abnormalities in granulocytic differentiation possibly as a result of hematopoietic stem cell differentiation imbalance induced by TGF-β1 and other growth factors produced by the tumor cells. TGF-β1 highlights a paradoxical shift in the regulation of clone formation and granulocytic differentiation of spleen hematopoietic stem cells.

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更新日期/Last Update: 1900-01-01