癌相关成纤维细胞促进胃癌细胞迁移与侵袭

周畅; 陈伟强; 王宇恒; 杨晓夏; 涂幸; 刘靖; 罗利

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癌相关成纤维细胞促进胃癌细胞迁移与侵袭

基础研究 | 更新时间：2023-11-01

- 癌相关成纤维细胞促进胃癌细胞迁移与侵袭
- Cancer Associated Fibroblasts Promote Migration and Invasion of Gastric Cancer Cells by Inducing Epithelial-mesenchymal Transition
- 中山大学学报（医学科学版） 2020年41卷第4期页码：501-508
- 作者机构：
  
  1.广东药科大学，生命科学与生物制药学院，广东广州 510006
  2.广东药科大学，护理学院，广东广州 510006
- 作者简介：
  
  周畅，博士，讲师，研究方向：肿瘤学，E-mail：zhouchang80@126.com
- 基金信息：
  
  国家自然科学基金(81901524);广东省自然科学基金(2018A0303130304;2018A030313579);广东省大学生创新创业训练项目(201810573041)
- DOI：
  中图分类号： R735.2
- 纸质出版日期：2020-07-15，
  
  收稿日期：2020-04-07，
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周畅,陈伟强,王宇恒等.癌相关成纤维细胞促进胃癌细胞迁移与侵袭[J].中山大学学报（医学科学版）,2020,41(04):501-508.

ZHOU Chang,CHEN Wei-qiang,WANG Yu-heng,et al.Cancer Associated Fibroblasts Promote Migration and Invasion of Gastric Cancer Cells by Inducing Epithelial-mesenchymal Transition[J].Journal of Sun Yat-sen University(Medical Sciences),2020,41(04):501-508.
周畅,陈伟强,王宇恒等.癌相关成纤维细胞促进胃癌细胞迁移与侵袭[J].中山大学学报（医学科学版）,2020,41(04):501-508. DOI：

ZHOU Chang,CHEN Wei-qiang,WANG Yu-heng,et al.Cancer Associated Fibroblasts Promote Migration and Invasion of Gastric Cancer Cells by Inducing Epithelial-mesenchymal Transition[J].Journal of Sun Yat-sen University(Medical Sciences),2020,41(04):501-508. DOI：

摘要

目的

本研究旨在探讨癌相关成纤维细胞（CAFs）对胃癌细胞迁移与侵袭能力的影响及作用机制。

方法

采用酶消化法分离培养正常成纤维细胞（NFs）及癌相关成纤维细胞（CAFs）并进行特征指标鉴定。收集两种细胞的条件培养基（NFs-CM、 CAFs-CM），分别作用于胃癌细胞系AGS及MGC803，利用细胞划痕实验检测胃癌细胞迁移能力；Transwell小室迁移及侵袭实验评价胃癌细胞迁移与侵袭能力；光学显微镜观察胃癌细胞形态变化；荧光定量PCR检测胃癌细胞中“上皮-间质”转化（EMT）相关指标的表达变化。

结果

我们成功分离培养NFs及CAFs；与NFs-CM 组相比，CAFs-CM组胃癌细胞的迁移与侵袭能力均增强（

0.05），胃癌细胞形态由扁圆的上皮细胞形态演变为梭形的间质细胞形态，胃癌细胞中上皮细胞标志E-钙粘蛋白（E-cadherin）表达降低，间质细胞标志波形蛋白（Vimentin）和 N-钙粘蛋白（N-cadherin）表达上升（

0.05）。

结论

CAFs可通过调节EMT进程促进胃癌细胞迁移与侵袭。

Abstract

Objective

To explore the effects of cancer associated fibroblasts (CAFs) on migration and invasion of Gastric cancer (GC) cells and the underlying mechanism.

Methods

The primary CAFs and the normal fibroblasts (NFs) were isolated from GC tissues and their matched adjacent normal gastric mucosa tissue respectively (

=3). The conditioned medium from cultured NFs (NFs-CM) and CAFs (CAFs-CM) were obtained and then incubated with the GC cell lines AGS and MGC803. GC cell migration and invasion were determined by wound healing assay and Transwell assay. Light microscopy was performed to observe the morphological changes of GC cells. Quantitative real-time PCR was employed to detect the changes in expression of epithelial mesenchymal transition (EMT) associated markers in GC cells.

Results

CAFs and NFs were successfully cultured and identified. Compared with NFs-CM

CAFs-CM accelerated migration and invasion of GC cells (all

0.05); showed more shuttle-like or spindle-like shape of GC cells; revealed decreased expression of E-cadherin

increased expression of Vimentin and N-cadherin in GC cells (all

0.05).

Conclusion

CAFs could enhance the migration and invasion of GC cells AGS and MGC803 via regulating EMT.

关键词

癌相关成纤维细胞胃癌迁移侵袭“上皮-间质”转化

Keywords

cancer associated fibroblasts (CAFs)gastric cancer (GC)migrationinvasionepithelial mesenchymal transition (EMT)

references

Thrift AP, El-Serag HB. Burden of gastric cancer[J]. Clin Gastroenterol Hepatol, 2020, 18(3): 534-542.

李金梅,刘艳茹,陈红,等.胃癌中LRG1的表达与肿瘤微血管生成的关系[J]. 广东医学, 2018, 39(19): 2903-2906.

Li JM, Liu YR, Chen H, et al. Relationship between LRG1 and tumor angiogenesis in gastric cancer tissue[J]. Guangdong Med, 2018, 39(19): 2903-2906.

Lin C, He H, Liu H, et al. Tumour-associated macrophages-derived CXCL8 d etermines immune evasion through autonomous PD-L1 expression in gastric cancer[J]. Gut， 2019, 68(10): 1764-1773.

葛曙雄,王涌.微小RNA与肿瘤微环境[J]. 新医学, 2016, 47(1): 7-11.

Ge SX, Wang Y. MicroRNAs and tumor microenvironment[J]. New Med, 2016, 47(1): 7-11.

Chen X, Song E. Turning foes to friends: targeting cancer-associated fibroblasts [J]. Nat Rev Drug Discov, 2019, 18(2): 99-115.

Kemi N, Eskuri M, Herva A, et al. Tumour-stroma ratio and prognosis in gastric adenocarcinoma[J]. Br J Cancer, 2018, 119(4): 435-439.

Gong J, Wang Y, Shu C. LncRNA CHRF promotes cell invasion and migration via EMT in gastric cancer[J]. Eur Rev Med Pharmacol Sci, 2020, 24(3): 1168-1176.

Pastushenko I, Blanpain C. EMT transition states during tumor progression and metastasis[J]. Trends Cell Biol, 2019, 29(3): 212-226.

Saitoh M. Involvement of partial EMT in cancer progression[J]. J Biochem, 2018, 164(4): 257-264.

Sun Y, Han C. Long Non-Coding RNA TMPO-AS1 promotes cell migration and invasion by sponging miR-140-5p and inducing SOX4-mediated EMT in gastric cancer[J]. Cancer Manag Res, 2020, 12: 1261-1268.

Mendonsa AM, Na TY, Gumbiner BM. E-cadherin in contact inhibition and cancer[J]. Oncogene, 2018, 37(35): 4769-4780.

Wang L, Li K, Wang C, et al. miR-107 regulates growth and metastasis of gastric cancer cells via activation of the PI3K-AKT signaling pathway by down-regulating FAT4[J]. Cancer Med, 2019, 8(11): 5264-5273.

Gheldof A, Berx G. Cadherins and epithelial-to-mesenchymal transition[J]. Prog Mol Biol Transl Sci, 2013, 116: 317-336.

Lambrechts D, Wauters E, Boeckx B, et al. Phenotype molding of stromal cells in the lung tumor microenvironment[J]. Nat Med, 2018, 24(8): 1277-1289.

Shan T, Chen S, Chen X, et al. Prometastatic mechanisms of CAF-mediated EMT regulation in pancreatic cancer cells[J]. Int J Oncol, 2017, 50(1): 121-128.

Wang H, Wei H, Wang J, et al. MicroRNA-181d-5p-Containing exosomes derived from CAFs promote EMT by regulating CDX2/HOXA5 in breast cancer[J]. Mol Ther Nucleic Acids, 2020, 19: 654-667.

Deng J, Yamashita H, Seto Y, et al. Increasing the number of examined lymph nodes is a prerequisite for improvement in the accurate evaluation of overall survival of node-negative gastric cancer patients[J]. Ann Surg Oncol, 2017, 24(3): 745-753.

Komohara Y, Takeya M. CAFs and TAMs: maestros of the tumour microenvironment[J]. J Pathol, 2017, 241(3): 313-315.

Fujita H, Ochuchida K, Nakata K, et al. Alpha-smooth muscle actin expressing stroma promotes an aggressive tumor biology in pancreatic ductal adenocarcinoma[J]. Pancreas, 2010, 39（8）: 1254-1262.

Ramirez-Montagut T, Blachere NE, Sviderskaya EV, et al. FAPalpha, a surface peptidase expressed during wound healing, is a tumor suppressor[J]. Oncogene, 2004, 23（32）: 5435-5446.

Gugnoni M, Sancisi V, Gandolfi G, et al. Cadherin-6 promotes EMT and cancer metastasis by restraining autophagy[J]. Oncogene, 2017, 36(5): 667-677.

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