[乳腺癌患者粒细胞分化异常及转化生长因子-β1的矛盾性转变]

[Abnormal granulocyte differentiation and the paradoxical switch of transforming growth factor-β1 in breast cancer patients].

作者信息

Pan Zhenzhen, Yao Minmin, Chen Yingge, Deng Jiuling, Yan Meiqiu, Gao Jianli

机构信息

College of Basic Medical Sciences, Hangzhou 310053, China.

Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2018 Jul 30;38(7):856-860. doi: 10.3969/j.issn.1673-4254.2018.07.14.

DOI:10.3969/j.issn.1673-4254.2018.07.14

PMID:33168499

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6765545/

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 ( < 0.05), while the eosinophils and its subpopulations were obviously decreased ( < 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 ( < 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.

CONCLUSIONS

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.

摘要

目的

分析乳腺癌患者粒细胞分化异常的特征，探讨转化生长因子-β1（TGF-β1）在造血干细胞（HSCs）粒细胞分化及肿瘤发展中的作用。

方法

收集52例浸润性导管癌患者和47例健康供者的血样。比较两组粒细胞分布情况，分析手术和放疗对粒细胞的影响。分析粒细胞异常与患者临床病理特征的关系。分离正常小鼠和荷瘤小鼠脾脏造血干细胞，用TGF-β1处理，比较髓系细胞集落形成情况，并用流式细胞术分析粒细胞比例。

结果

乳腺癌患者白细胞（WBC）计数、中性粒细胞、总粒细胞、WBC中粒细胞比例及中性粒细胞/淋巴细胞比值（NLR）显著升高（<0.05），而嗜酸性粒细胞及其亚群明显降低（<0.05）。克隆形成实验表明，荷瘤小鼠脾脏细胞中CFU-GM、BFU-E和CFU-M集落数量显著多于正常小鼠（<0.05）。TGF-β1处理明显抑制正常小鼠脾脏造血干细胞克隆形成，但显著促进荷瘤小鼠脾脏造血干细胞增殖和粒细胞分化。