小鼠乳腺癌诱导转移前肺组织微环境的改变

doi:10.6040/j.issn.1671-7554.0.2021.1392

摘要/Abstract

摘要： 目的探讨乳腺癌转移前肺组织的变化及其转移的可能机制。方法将20只雌性BALB/c 小鼠随机分为实验组和对照组,每组10只。实验组小鼠腹壁上第4对乳腺处注射乳腺癌细胞悬液,对照组小鼠在相同部位注射等量磷酸盐缓冲液(PBS)。在注射后第0、7、14、21和28天,每组分别取2只小鼠处死,将肺组织用4%多聚甲醛固定,石蜡包埋切片。采用HE染色法观察小鼠肺组织形态学变化,免疫组织化学染色法检测肺组织中纤维连接蛋白、Ⅰ型胶原和CD31的表达水平;应用Image-Pro Plus 6.0软件进行纤维连接蛋白、Ⅰ型胶原和CD31表达的半定量分析。结果与对照组比较,实验组小鼠肿瘤体积不断增长,体质量呈下降趋势;HE染色结果显示,肺组织炎性细胞增多,正常生理结构被破坏;免疫组织化学染色结果显示,对照组与实验组纤维连接蛋白、Ⅰ型胶原和CD31的表达量总体差异均有统计学意义(P均<0.001)。结论在转移前期,乳腺恶性肿瘤能够调节肺组织微环境,诱导肺组织发生炎症性改变,促进转移性肿瘤的发生。

关键词: 乳腺癌, 预转移, 肺, Ⅰ型胶原, 血管, 动物模型

Abstract: Objective To explore lung tissue changes and possible mechanisms before breast cancer metastasis. Methods A total of 20 female BALB/c mice were randomly divided into the experimental group and control group, with 10 mice in either group. Breast cancer cells were suspended in serum free medium and injected into the fourth pair of breast glands on the abdominal wall of mice in the experimental group, while equal amounts of PBS was injected into the same site in mice in the control group. On day 0, 7, 14, 21 and 28 after injection, 2 mice from both groups were sacrificed, their lung tissues were fixed with 4% paraformaldehyde, embedded in paraffin and sectioned. The histopathological changes were observed with HE staining; the expressions of fibronectin, type I collagen and CD31 were detected with immunohistochemistry and semi-quantitatively analyzed with Image-Pro Plus 6.0 software system. Results Compared with the control group, the experimental group had increased tumor volume but decreased weight. HE staining showed the number of inflammatory cells in lung tissue increased and the normal physiological structure was destroyed in the experimental group. Immunohistochemistry showed significant differences in the expressions of fibronectin, type Ⅰ collagen and CD31 between the two groups(all P<0.001). Conclusion In the pre-metastatic stage, malignant breast tumor can change the microenvironment of lung tissue, induce pulmonary inflammation response and promote the metastasis of tumor.

Key words: Breast cancer, Pre-metastatic, Lung, Type I collagen, Vessel, Animal model

中图分类号:

R737.9

赵婷婷,齐亚娜,张颖,袁冰,韩明勇. 小鼠乳腺癌诱导转移前肺组织微环境的改变[J]. 山东大学学报 (医学版), 2022, 60(4): 24-29.

ZHAO Tingting, QI Yana, ZHANG Ying, YUAN Bing, HAN Mingyong. Mouse breast cancer induces changes of the microenvironment in pre-metastatic lung tissue[J]. Journal of Shandong University (Health Sciences), 2022, 60(4): 24-29.

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