|Table of Contents|

Expression of Claudin-1 protein in gastric cancer tissues and cells and its effect on cancer cell proliferation,invasion and migration after promoting its expression

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2021 06
Page:
934-940
Research Field:
Publishing date:

Info

Title:
Expression of Claudin-1 protein in gastric cancer tissues and cells and its effect on cancer cell proliferation,invasion and migration after promoting its expression
Author(s):
GUO Xiaoguang; TANG Zhirong; HAN Ying; LIAO Wenhua; ZHANG Tao
Department of Clinicopathology,Nanchong Central Hospital,Sichuan Nanchong 637000,China.
Keywords:
Claudin-1; gastric cancer; proliferation; invasion; migration; EMT
PACS:
R735.2
DOI:
10.3969/j.issn.1672-4992.2021.06.006
Abstract:
Objective:To study the expression of tight junction transmembrane protein (Claudin-1) in gastric cancer tissues and its effect on the biological behavior of gastric cancer cells and the ability of subcutaneous tumor formation in nude mice.Methods:The cancer tissues and adjacent tissues of 50 patients with gastric cancer were collected,and the expression level of Claudin-1 in tissues was detected by RT-qPCR and immunohistochemistry.RT-qPCR and Western Blot were used to detect the expression level of Claudin-1 in human gastric cancer cell line MKN45,human gastric carcinoma SGC7901 cell line,human gastric carcinoma MKN28 cell line and normal human immortalized gastric epithelial cells (GES-1).Claudin-1 was overexpressed in human gastric cancer cell line SGC7901 by lentivirus.The cells were divided into control group (untransfected),NC group (transfected with lentiviral vector) and Claudin-1 group (transfected with Claudin-1 overexpressing lentivirus).Cell Counting Kit-8 (CCK-8),Transwell test,and scratch test were used to detect changes in gastric cancer cell proliferation,invasion,and migration ability.Western Blot and immunofluorescence experiments were used to detect the expression of Claudin-1 on epithelial-mesenchymal transition (EMT) marker proteins E-cadherin and N-cadherin.Ten 4-week-old male BALB/c nude mice were injected subcutaneously with Claudin-1 overexpressing lentivirus-treated SGC7901 cells to construct a xenograft model,and the effect of Claudin-1 overexpression on subcutaneous xenografts was studied.Kaplan-Meier website was used to analysis the relationship between Claudin-1 expression and patient survival.Results:Immunohistochemical results showed that the expression level of Claudin-1 in gastric cancer tissue was significantly lower than that in adjacent tissues (P＜0.05).Overexpression of Claudin-1 could significantly inhibit the proliferation,invasion and migration ability of SGC7901 cells (P＜0.05).At the same time,the expression of E-cadherin was increased and the expression of N-cadherin was decreased.Overexpression of Claudin-1 in a nude mouse xenograft model can significantly inhibit the growth of subcutaneous xenografts (P＜0.05).Patients with high expression of Claudin-1 survive longer than patients with low expression of Claudin-1.Conclusion:Claudin-1 is underexpressed in gastric cancer tissues.Overexpression of Claudin-1 inhibits the proliferation,invasion,migration,and EMT of gastric cancer cells and inhibits the ability of subcutaneous tumor formation in nude mice.Claudin-1 high expression promotes good prognosis for patients.

References:

［1］RUGGE M,GENTA RM,DI MARIO F,et al.Gastric cancer as preventable disease［J］.Clinical Gastroenterology and Hepatology,2017,15(12):1833-1843.
［2］TSUKITA S,TANAKA H,TAMURA A.The claudins:from tight junctions to biological systems［J］.Trends in Biochemical Sciences,2019,44(2):141-152.
［3］CHE J,YANG Y,XIAO J,et al.Decreased expression of claudin-3 is associated with a poor prognosis and EMT in completely resected squamous cell lung carcinoma［J］.Tumor Biology,2015,36(8):6559-6568.
［4］MOLDVAY J,FBIN K,JCKEL M,et al.Claudin-1 protein expression is a good prognostic factor in non-small cell lung cancer,but only in squamous cell carcinoma cases［J］.Pathology & Oncology Research,2017,23(1):151-156.
［5］LIU M,YANG J,ZHANG Y,et al.ZIP4 promotes pancreatic cancer progression by repressing ZO-1 and Claudin-1 through a ZEB1-dependent transcriptional mechanism［J］.Clinical Cancer Research,2018,24(13):3186-3196.
［6］MAJER A,BLANCHARD AA,MEDINA S,et al.Claudin 1 expression levels affect miRNA dynamics in human basal-like breast cancer cells［J］.DNA and Cell Biology,2016,35(7):328-339.
［7］MASTERSON JC,BIETTE KA,HAMMER JA,et al.Epithelial HIF-1 α/claudin-1 axis regulates barrier dysfunction in eosinophilic esophagitis［J］.Journal of Clinical Investigation,2019,129(8):3224-3235.
［8］SUH Y,YOON CH,KIM RK,et al.Claudin-1 induces epithelial-mesenchymal transition through activation of the c-Abl-ERK signaling pathway in human liver cells［J］.Oncogene,2017,36(8):1167-1168.
［9］ 项航,王伟,林文楚.Claudin 蛋白在胃癌中的作用及其临床研究进展［J］.中国肿瘤生物治疗杂志,2019,26(8):910-915. XIANG H,WANG W,LIN WC.Role of Claudin protein in gastric cancer and its clinical research progress［J］.Chin J Cancer Biother,2019,26(8):910-915.
［10］JIA X,CUI J,MENG X,et al.Malignant transformation of human gastric epithelium cells via reactive oxygen species production and Wnt/β-catenin pathway activation following 40-week exposure to ochratoxin A［J］.Cancer Letters,2016,372(1):36-47.
［11］TABARIS S,SIEGEL PM.The role of claudins in cancer metastasis［J］.Oncogene 2017,36(9):1176-1190.
［12］ZHOU B,MOODIE A,BLANCHARD AAA,et al.Claudin 1 in breast cancer:new insights［J］.Journal of Clinical Medicine,2015,4(12):1960-1976.
［13］ABDELWAHAB MM,ABDELRAHMAN AE.Immunohistochemical expression of Bmi-1,S100A4,and claudin-1 in breast cancer［J］.Egyptian Journal of Pathology,2017,37(1):82-90.
［14］MAHMOUD AS,FOUAD EM,AHMED RZ,et al.Snail-1,ALDH1,and claudin-1 tissue protein expression in patients with colorectal cancer:clinicopathological and prognostic implications［J］.Egyptian Journal of Pathology,2018,38(2):249-259.
［15］WANG H,YANG X.The expression patterns of tight junction protein claudin-1,-3,and -4 in human gastric neoplasms and adjacent non-neoplastic tissues［J］.Int J Clin Exp Pathol,2015,8(1):881-887.
［16］HMLINEN L,SOINI Y,PASONEN-SEPPNEN S,et al.Alterations in the expression of EMT-related proteins claudin-1,-4 and -7,E-cadherin,TWIST 1 and ZEB 1 in oral lichen planus［J］.Journal of Oral Pathology & Medicine,2019,48(8):735-744.
［17］BRABLETZ T,KALLURI R,NIETO MA,et al.EMT in cancer［J］.Nature Reviews Cancer,2018,18(2):128-134.
［18］PAN L,YANG Z,LIU S,et al.Clinical significance of claudin-1 in gastric cancer:a meta-analysis［J］.Int J Clin Exp Med,2019,12(1):26-37.
［19］IZRAELY S,SAGI-ASSIF O,KLEIN A,et al.The metastatic microenvironment:Claudin-1 suppresses the malignant phenotype of melanoma brain metastasis［J］.International Journal of Cancer,2015,136(6):1296-1307.

Memo

Memo:
四川省科技厅面上项目（编号：2018JY0417）;南充市科学技术和知识产权局省级科技计划项目(编号：2018JY0416)
Last Update: 1900-01-01