微信公众号

官网二维码
中国癌症防治杂志

中国癌症防治杂志 ›› 2025, Vol. 17 ›› Issue (6): 730-738.doi: 10.3969/j.issn.1674-5671.2025.06.11

• 论著 • 上一篇    下一篇

M2型肿瘤相关巨噬细胞通过调控CTHRC1促进胃癌MKN⁃45细胞增殖及上皮⁃间质转化

  

  1. 北京大学肿瘤医院内蒙古医院（内蒙古医科大学附属肿瘤医院）检验科
  • 出版日期:2025-12-25 发布日期:2026-02-02
  • 通讯作者: 赵慧英 E-mail：zhy19860709@163.com
  • 基金资助:
    内蒙古自治区卫生健康委2023年首府地区公立医院高水平临床专科建设科研项目（2023SGGZ072?04）；北京大学肿瘤医院内蒙古医院“青苗”人才计划项目（QM202318）

M2⁃type tumor⁃associated macrophages promote the proliferation and epithelial⁃mesenchymal transition of gastric cancer MKN⁃45 cells by regulating CTHRC1 expression

  • Online:2025-12-25 Published:2026-02-02

PDF (PC)

30

赞

摘要： 目的 探讨M2型肿瘤相关巨噬细胞（tumor⁃associated macrophages,TAMs）对胃癌细胞增殖及上皮⁃间质转化（epithelial⁃mesenchymal transition, EMT）的影响及潜在机制。方法 体外诱导THP⁃1细胞分化为M2型巨噬细胞，经胃癌MKN⁃45细胞来源条件培养基处理，获得M2型TAMs（M2⁃TAMs）。将M2⁃TAMs与MKN⁃45细胞共培养（MKN⁃45组和M2⁃TAMs /MKN⁃45组）；另采用siRNA技术沉默MKN⁃45细胞中胶原三股螺旋重复蛋白1（collagen triple helix repeat containing 1，CTHRC1）后与或不与M2⁃TAMs共培养（si⁃NC组、si⁃CTHRC1组、M2⁃TAMs/si⁃NC组和M2⁃TAMs/si⁃CTHRC1组）。采用CCK⁃8、集落形成、Transwell和划痕实验分别检测细胞增殖、侵袭和迁移能力；ELISA法检测细胞上清液中基质金属蛋白酶2（matrix metalloproteinase 2，MMP2）和基质金属蛋白酶9（matrix metalloproteinase 9，MMP9）含量；qRT⁃PCR检测细胞中CTHRC1 mRNA表达水平；Western blot检测细胞中E⁃cadherin、N⁃cadherin、Vimentin和CTHRC1的蛋白表达水平。结果 与MKN⁃45组比较，M2⁃TAMs/MKN⁃45组细胞的增殖、迁移和侵袭能力显著升高（均P<0.05），MMP2和MMP9含量增加（均P<0.01），E⁃cadherin表达降低（P<0.001），N⁃cadherin、Vimentin、CTHRC1的表达升高（均P<0.01）。与si⁃NC组比较，si⁃CTHRC1组细胞增殖、迁移和侵袭能力降低（均P<0.05），E⁃cadherin表达升高（P<0.001），CTHRC1、N⁃cadherin、Vimentin表达降低（均P<0.01）。与M2⁃TAMs/si⁃NC组比较，M2⁃TAMs/si⁃CTHRC1组细胞增殖、迁移和侵袭能力降低（均P<0.05），E⁃cadherin表达升高（P<0.001），而CTHRC1、N⁃cadherin、Vimentin表达水平降低（均P<0.01）。结论 M2⁃TAMs可能通过上调CTHRC1表达，促进胃癌MKN⁃45细胞增殖及EMT。

关键词: 肿瘤相关巨噬细胞, 胃癌, 胶原三股螺旋重复蛋白1, 增殖, 上皮?间质转化

Abstract: Objective To investigate the effects of M2⁃type tumor⁃associated macrophages (TAMs) on the proliferation of gastric cancer cells and epithelial⁃mesenchymal transition (EMT) , along with possible mechanisms. Methods THP⁃1 cells were differentiated into M2⁃type macrophages in vitro and treated with conditioned medium from gastric cancer MKN⁃45 cells to obtain M2⁃type TAMs (M2⁃TAMs). M2⁃TAMs were co⁃cultured with MKN⁃45 cells (MKN⁃45 group and M2⁃TAMs/MKN⁃45 group). In addition, siRNA technology was used to silence collagen triple helix repeat containing 1 (CTHRC1) in MKN⁃45 cells, the cells were co⁃cultured with or without M2⁃TAMs (si⁃NC group, si⁃CTHRC1 group, M2⁃TAMs/si⁃NC group, and M2⁃TAMs/si⁃CTHRC1 group). Cell proliferation, invasion and migration abilities were detected by CCK⁃8, colony formation, Transwell and scratch test. The levels of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) in cell supernatant were detected by ELISA. qRT⁃PCR was used to detect the expression level of CTHRC1 mRNA in cells. Western blot was used to detect the protein expression levels of E⁃cadherin, N⁃cadherin, Vimentin and CTHRC1. Results Compared with the MKN⁃45 group, the M2⁃TAMs/MKN⁃45 group showed significantly increased cell proliferation, migration and invasion abilities (all P<0.05), upregulated MMP2 and MMP9 levels (all P<0.01), decreased E⁃cadherin expression(P<0.001), and increased N⁃cadherin, Vimentin and CTHRC1 expression (all P<0.01). Compared with the si⁃NC group, the si⁃CTHRC1 group exhibited significantly reduced cell proliferation, migration and invasion abilities (all P<0.05), increased E⁃cadherin expression (P<0.001), and decreased CTHRC1, N⁃cadherin and Vimentin expression (all P<0.01). Compared with the M2⁃TAMs/si⁃NC group, the M2⁃TAMs/si⁃CTHRC1 group showed significantly decreased cell proliferation, migration and invasion abilities (all P<0.05), increased E⁃cadherin expression (P<0.001), and decreased CTHRC1, N⁃cadherin and Vimentin expression (all P<0.01). Conclusions M2⁃type TAMs may promote the proliferation and EMT of gastric cancer MKN⁃45 cells by upregulating CTHRC1 expression.

Key words: Tumor?associated macrophages, Gastric cancer, Collagen triple helix repeat containing 1, Proliferation, Epithelial?mesenchymal transition

中图分类号: 

  •