Eftect of Lewis lung cancer on mouse intestinal stem cells and their microenvironment

Zhenni XU; Jing OU; Yu WANG; Xudan LEI; Lingxiao HUANG; Tao WANG; Fengchao WANG; Jining GAO; Junping WANG; Yongping SU; Dengqun LIU

doi:10.16016/j.1000-5404.202002046

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Eftect of Lewis lung cancer on mouse intestinal stem cells and their microenvironment

Basic Medicine | 更新时间：2026-01-09

- Eftect of Lewis lung cancer on mouse intestinal stem cells and their microenvironment
- Journal of Third Military Medical University Vol. 42, Issue 12, Pages: 1155-1163(2020)
- 作者机构：
  
  1.400038 重庆, 陆军军医大学(第三军医大学)军事预防医学系:防原医学教研室, 全军复合伤研究所, 创伤、烧伤与复合伤国家重点实验室, 重庆市纳米医学工程研究中心
  2.400038 重庆, 陆军军医大学(第三军医大学)军事预防医学系: 火箭军医学教研室
  3.610041 成都, 四川省肿瘤医院.研究所, 四川省癌症防治中心, 电子科技大学医学院, 放射肿瘤学四川省重点实验室
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81673089);the General Program of National Natural Science Foundation of China(81874255);the Applied Basic Science Research Plan of Science and Technology Department of Sichuan Province(2020YJ0458);the Research Program of Sichuan Cancer Hospital(YBR2019003)
- DOI：10.16016/j.1000-5404.202002046
  CLC： R322.45;R730.23;R734.2
- Received：10 February 2020，
  
  Revised：2020-03-16，
  
  Published：30 June 2020
- 稿件说明：
移动端阅览
Zhenni XU, Jing OU, Yu WANG, et al. Eftect of Lewis lung cancer on mouse intestinal stem cells and their microenvironment[J]. Journal of Third Military Medical University, 2020, 42(12): 1155-1163.
DOI：

Zhenni XU, Jing OU, Yu WANG, et al. Eftect of Lewis lung cancer on mouse intestinal stem cells and their microenvironment[J]. Journal of Third Military Medical University, 2020, 42(12): 1155-1163. DOI： 10.16016/j.1000-5404.202002046.

摘要

目的

探讨Lewis肺腺癌(Lewis lung cancer

LLC)对小鼠肠道干细胞及其微环境的影响。

方法

比较不同接种方式(皮下接种和静脉移植)在C57BL /6J小鼠肺部形成肺腺癌的能力差异。通过HE、BrdU免疫染色和qPCR检测LLC对肠道形态、增殖动力学、肠道干细胞及其微环境相关基因、肠上皮细胞紧密连接及炎症因子表达的影响。使用EdU染色评价LLC条件培养基(LLC-CM)对IEC-6细胞增殖的影响。使用LLC细胞和LLC-CM观察肺腺癌对肠类器官生长的影响。

结果

静脉移植LLC细胞较皮下接种荷瘤更易在小鼠肺部形成肺腺癌。肺腺癌导致绒毛和隐窝长度较对照组显著增加(

0.01)

BrdU阳性细胞数量和Ki67基因mRNA水平显著高于对照组(

0.05)。LLC-CM可增加EdU阳性IEC-6细胞数量(

0.05)。肺腺癌小鼠肠组织中肠道干细胞标志物基因(Lgr5、Olfm4、Axin2)表达水平显著下降

微环境相关基因(Wnt3)表达水平降低(

0.05)。肺腺癌引起肠上皮ZO-1免疫染色以及ZO-1和OCLN mRNA表达显著降低

IL-1β和TNF-α的mRNA含量显著增加(

0.05)。LLC细胞和LLC-CM均抑制肠类器官生长。

结论

Lewis肺腺癌能够破坏肠道干细胞及其微环境

为肺癌与肠道交互作用提供了新的实验依据。

Abstract

Objective

To investigate the changes in intestinal stem cells (ISCs) and their microenvironment in a mouse model bearing Lewis lung cancer (LLC).

Methods

We compared the tumorigenicity of LLC cells in mice following subcutaneous transplantation and tail vein injection of the cells. HE staining

immunostaining and qPCR were used to analyze how LLC affected the intestinal morphology

cell proliferation dynamics

ISCs and their niche-related genes

intestinal epithelial cell tight junctions

and the expression of inflammatory cytokines.We also evaluated the effect of LLC conditioned medium (LLC-CM) onthe proliferation of cultured IEC-6 cells using EdU staining

and observed the growth of intestinal enteroids co- cultured with LLC cells or in the presence of LLC-CM.

Results

Tail vein injection more efficiently induced the formation of LLC in mice than subcutaneous transplantation of LLC cells.The mice bea

ring LLC exhibited significantly increased length of the mucosal villi and depth of the crypts (

0.01)

and had more BrdU- positive cells and a higher level of Ki67 mRNA expression in the intestines as compared with the control mice (

0.05).LLC-CM obviously promoted the incorporation of EdU in IEC-6 cells.The tumor-bearing mice showed significantly decreased expression of ISC markers and microenvironment-related genes (including Lgr5

Olfm4

Axin2

and Wnt3) in the intestines (

0.05)

where the staining signals of ZO-1 and the mRNA expression of TJP1 and OCLN was significantly decreased and the mRNA levels of IL-1β and TNF-α were markedly increased (

0.05).Both LLC and LLC-CM significantly inhibited the growth of cultured mouse intestinal organoids

Conclusion

LLC disrupts the ISCs and their niche in mice

which provides new evidence of the interaction between lung cancer and the gastrointestinal tract.

关键词

Keywords

references

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Related Institution

Key Laboratory of Radiation Oncology of Sichuan Province, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine of University of Electronic Science and Technology of China

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