HPA通过上调MCP-1/CCR2促进胃癌发生侵袭和转移

doi:10.11904/j.issn.1002-3070.2023.04.006

实用肿瘤学杂志 ›› 2023, Vol. 37 ›› Issue (4): 329-336.doi: 10.11904/j.issn.1002-3070.2023.04.006

HPA通过上调MCP-1/CCR2促进胃癌发生侵袭和转移

付鑫雅¹, 胡灵丹¹, 张志坚¹, 马秀梅²

1.内蒙古医科大学(呼和浩特 010000);
2.内蒙古医科大学附属医院病理科

收稿日期:2022-03-28 修回日期:2022-10-12 出版日期:2023-08-28 发布日期:2023-12-12
通讯作者: 马秀梅,E-mail:1771120626@qq.com
作者简介:付鑫雅,女,(1996-),硕士研究生,从事胃癌相关的研究。
基金资助:
内蒙古自治区自然科学基金项目(编号:2018MS08021)

HPA promotes the invasion and metastasis of human gastric cancer cells by up-regulating MCP1/CCR2

FU Xinya¹, HU Lingdan¹, ZHANG Zhijian¹, MA Xiumei²

1. Inner Mongolia Medical University, Hohhot 010000, China;
2. Department of Pathology, Affiliated Hospital of Inner Mongolia Medical University

Received:2022-03-28 Revised:2022-10-12 Online:2023-08-28 Published:2023-12-12

摘要/Abstract

摘要： 目的检测乙酰肝素酶(HPA)、单核细胞趋化因子-1(MCP-1)和趋化因子受体2(CCR2)在人胃癌中的表达,探讨HPA诱导人胃癌细胞发生侵袭和转移的分子机制。方法免疫组织化学方法检测74例人胃癌组织中HPA、MCP-1和CCR2蛋白的表达。培养人胃癌MGC803细胞、MGC803-HPA细胞(过表达HPA蛋白细胞株)、SGC7901细胞和SGC7901-HPA(-)细胞(敲低HPA蛋白细胞株)。MGC803细胞和SGC7901细胞作为实验组,MGC803-HPA细胞和SGC7901-HPA(-)作为对照组,MTT实验检测CCR2抑制剂(RS504393)作用于人胃癌MGC803-HPA细胞的最适抑制浓度,Western blot实验检测人胃癌细胞中各种蛋白的表达,划痕实验和Transwell侵袭实验检测细胞迁移和侵袭能力。结果人胃癌组织中HPA、MCP-1/CCR2蛋白阳性表达与人胃癌发病部位、分化程度、侵袭深度以及淋巴结转移相关(P＜0.05)。人胃癌组织中HPA蛋白表达与MCP-1/CCR2蛋白表达呈正相关(P＜0.05)。HPA过表达可促进细胞迁移和侵袭(P＜0.05),CCR2抑制剂RS504393能抑制胃癌细胞中因HPA过表达所增强的迁移和基质侵袭能力(P＜0.05)。结论人胃癌中HPA蛋白是诱导MCP-1/CCR2蛋白表达的上游因子,HPA通过上调MCP-1/CCR2蛋白表达诱导人胃癌发生侵袭和转移。

关键词: 胃癌, 乙酰肝素酶, 单核细胞趋化因子-1, 趋化因子受体2, 侵袭, 转移

Abstract: Objective The aim of this study was to investigate the expression of heparanase(HPA), monocyte chemokine-1(MCP-1)and chemokine receptor 2(CCR2)in human gastric cancer, and to explore the molecular mechanism of HPA induced invasion and metastasis of human gastric cancer cells. Methods Immunohistochemical method was used to detect the expression of HPA, MCP-1 and CCR2 proteins in 74 cases of human gastric cancer tissues. Human gastric cancer MGC803 cells, MGC803-HPA cells(HPA protein overexpressing cell line), SGC7901 cells, and SGC7901-HPA(-)cells(HPA protein knockdown cell line)were cultured. MGC803 cells and SGC7901 cells were used as the experimental group, MGC803-HPA cells and SGC7901-HPA(-)cells were used as the control group. MTT experiment was used to detect the optimal inhibitory concentration of CCR2 inhibitor(RS504393)in MGC803-HPA cells. Western blot experiment was used to detect the expression of various proteins in human gastric cancer cells. The scratch experiment and Transwell invasion assay were used to detect the abilities of migration and invasion in human gastric cancer cells. Results The positive expression of HPA and MCP-1/CCR2 proteins in human gastric cancer tissues was closely related to the location, degree of differentiation, depth of invasion and lymph node metastasis of human gastric cancer(P＜0.05). There is a positive correlation between HPA protein expression and MCP-1/CCR2 protein expression in human gastric cancer tissues(P＜0.05). HPA overexpression could promote cell migration and invasion(P＜0.05), and the CCR2 inhibitor RS504393 could inhibit the migration and matrix invasion ability enhanced by HPA overexpression in gastric cancer cells(P＜0.05). Conclusion HPA protein is an upstream factor that induces the expression of MCP-1/CCR2 protein in human gastric cancer. HPA induces invasion and metastasis of human gastric cancer by up-regulating MCP-1/CCR2 protein expression.

Key words: Gastric cancer, Heparanase, Monocyte chemokine-1, Chemokine receptor 2, Invasion, Metastasis

中图分类号:

R737.9

付鑫雅, 胡灵丹, 张志坚, 马秀梅. HPA通过上调MCP-1/CCR2促进胃癌发生侵袭和转移[J]. 实用肿瘤学杂志, 2023, 37(4): 329-336.

FU Xinya, HU Lingdan, ZHANG Zhijian, MA Xiumei. HPA promotes the invasion and metastasis of human gastric cancer cells by up-regulating MCP1/CCR2[J]. Journal of Practical Oncology, 2023, 37(4): 329-336.

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http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/Y2023/V37/I4/329

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HPA通过上调MCP-1/CCR2促进胃癌发生侵袭和转移

HPA promotes the invasion and metastasis of human gastric cancer cells by up-regulating MCP1/CCR2

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