摘要
目的研究不同周龄MMTV-PyMT乳腺癌转基因小鼠的致瘤特性及肿瘤微环境中免疫细胞的组成变化。方法准备8组在4、6、8、10、12、14、16、18周龄的MMTV-PyMT雌性小鼠(以FVB小鼠为背景)以及1组8周龄FVB雌性小鼠,对其血常规进行检测,通过组织病理学切片观察乳腺的病理变化及肺转移情况,通过流式细胞术分析血液、脾、肿瘤中的免疫细胞。结果MMTV-PyMT小鼠4~6周龄时乳腺导管出现腺管样病变,8~9周龄时导管部分长至生长边界,此后逐渐突破腺体边界,在8~12周龄时形成早期乳腺癌,在10~14周龄时出现晚期乳腺癌的特征。在12周龄时部分小鼠肺部分出现可见转移病灶,14周龄肺部转移灶明显增多;随着周龄增长,小鼠血液中白细胞、中性粒细胞、血小板逐渐增多,而淋巴细胞、红细胞则呈逐渐下降趋势;流式细胞术提示随着周龄增长,小鼠脾、肿瘤中T细胞比例逐渐下降,血液、脾、肿瘤中MDSCs逐渐增加,肿瘤中NK细胞也逐渐增加。结论本研究对不同周龄MMTV-PyMT小鼠模型的血常规、病理及组织中的免疫细胞进行分析,为乳腺癌恶性进展过程中肿瘤免疫微环境的动态变化提供新视角。
Objective This study aimed to investigate the tumorigenic properties of MMTV-PyMT breast cancer transgenic mice at different ages(in weeks)and the changes in the composition of immune cells in the tumor microenvironment.Methods Eight groups of 4,6,8,10,12,14,16 and 18 weeks of age MMTV-PyMT female mice(FVB mice as the background)and one group of 8 weeks of FVB female mice were prepared for routine blood testing,the pathological changes of the mammary gland and lung metastases were observed by histopathological sections,and the immune cells in blood,spleen,and tumor were analyzed by flow cytometry.Results MMTV-PyMT mice showed adenular ductal lesions at 4~6 weeks of age;the ductal portion expanded to the growth boundary at 8~9 weeks of age,and then gradually broke through the glandular boundary to form early breast cancer at 8~12 weeks of age,and advanced breast cancer at 10~14 weeks of age.At 12 weeks of age,metastases were visible in the lungs of some mice,and at 14 weeks of age,the number of metastases in the lungs increased significantly.As the age of the mice increased,the number of white blood cells,neutrophils,and platelets in their blood increased gradually,while the lymphocytes and erythrocytes showed a gradual downward trend.Flow cytometry showed that with the increase in age,the proportion of T cells in the spleen and tumor gradually decreased,the MDSCs in the blood,spleen,and tumor gradually increased,and the NK cells in the tumor also gradually increased.Conclusions This study analyzed routine blood tests,pathology,and immune cells in the tissues of MMTV-PyMT mouse models of different weeks of age,providing a novel perspective on the dynamic alterations of the tumor immune microenvironment during the malignant progression of breast cancer.
作者
林晓晨
龚丽红
郭迎雪
金璐
陈梦芸
王鹏皓
余翠
傅惠英
寿旗扬
LIN Xiaochen;GONG Lihong;GUO Yingxue;JIN Lu;CHEN Mengyun;WANG Penghao;YU Cui;FU Huiying;SHOU Qiyang(School of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou 310053,China;Second Clinical Hospital of Zhejiang Chinese Medical University,Hangzhou 310053,China;Jinhua Academy of Zhejiang Chinese Medical University,Hangzhou 310053,China)
出处
《中国实验动物学报》
北大核心
2025年第7期935-946,共12页
Acta Laboratorium Animalis Scientia Sinica
基金
国家自然科学基金(82274175,82174026)
国家中医药管理局科技司-浙江省中医药管理局共建科技计划项目(GZY-ZJ-KJ-23069)。
关键词
MMTV-PyMT转基因小鼠
乳腺癌
肺转移
肿瘤微环境
MMTV-PyMT transgenic mice
breast cancer
lung metastases
tumor microenvironment Conflicts of Interest:The authors declare no conflict of interest
