Cargando…

Downregulation of CD147 expression alters cytoskeleton architecture and inhibits gelatinase production and SAPK pathway in human hepatocellular carcinoma cells

BACKGROUND: CD147 plays a critical role in the invasive and metastatic activity of hepatocellular carcinoma (HCC) cells by stimulating the surrounding fibroblasts to express matrix metalloproteinases (MMPs). Tumor cells adhesion to extracellular matrix (ECM) proteins is the first step to the tumor m...

Descripción completa

Detalles Bibliográficos
Autores principales: Qian, Ai-Rong, Zhang, Wei, Cao, Jian-Ping, Yang, Peng-Fei, Gao, Xiang, Wang, Zhe, Xu, Hui-Yun, Weng, Yuan-Yuan, Shang, Peng
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2572039/
https://www.ncbi.nlm.nih.gov/pubmed/18847500
http://dx.doi.org/10.1186/1756-9966-27-50
_version_ 1782160234474635264
author Qian, Ai-Rong
Zhang, Wei
Cao, Jian-Ping
Yang, Peng-Fei
Gao, Xiang
Wang, Zhe
Xu, Hui-Yun
Weng, Yuan-Yuan
Shang, Peng
author_facet Qian, Ai-Rong
Zhang, Wei
Cao, Jian-Ping
Yang, Peng-Fei
Gao, Xiang
Wang, Zhe
Xu, Hui-Yun
Weng, Yuan-Yuan
Shang, Peng
author_sort Qian, Ai-Rong
collection PubMed
description BACKGROUND: CD147 plays a critical role in the invasive and metastatic activity of hepatocellular carcinoma (HCC) cells by stimulating the surrounding fibroblasts to express matrix metalloproteinases (MMPs). Tumor cells adhesion to extracellular matrix (ECM) proteins is the first step to the tumor metastasis. MMPs degrade the ECM to promote tumor metastasis. The aim of this study is to investigate the effects of small interfering RNA (siRNA) against CD147 (si-CD147) on hepatocellular carcinoma cells' (SMMC-7721) architecture and functions. METHODS: Flow cytometry and western blot assays were employed to detect the transfection efficiency of si-CD147. Confocal microscopy was used to determine the effects of si-CD147 on SMMC-7721 cells' cytoskeleton. Invasion assay, gelatin zymography and cell adhesion assay were employed to investigate the effects of si-CD147 on SMMC-7721 cells' invasion, gelatinase production and cell adhesive abilities. Western blot assay was utilized to detect the effects of si-CD147 on focal adhesion kinase (FAK), vinculiln and mitogen-activated protein kinase (MAPK) expression in SMMC-7721 cells. RESULTS: Downregulation of CD147 gene induced the alteration of SMMC-7721 cell cytoskeleton including actin, microtubule and vimentin filaments, and inhibited gelatinase production and expression, cells invasion, FAK and vinculin expression. si-CD147 also blocked SMMC-7721 cells adhesion to collagen IV and phosphorylation level of SAPK/JNKs. SAPK/JNKs inhibitor SP600125 inhibited gelatinase production and expression. CONCLUSION: CD147 is required for normal tumor cell architecture and cell invasion. Downregulation of CD147 affects HCC cell structure and function. Moreover, the alteration of cell behavior may be related to SAPK/JNK Pathway. siRNA against CD147 may be a possible new approach for HCC gene therapy.
format Text
id pubmed-2572039
institution National Center for Biotechnology Information
language English
publishDate 2008
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-25720392008-10-24 Downregulation of CD147 expression alters cytoskeleton architecture and inhibits gelatinase production and SAPK pathway in human hepatocellular carcinoma cells Qian, Ai-Rong Zhang, Wei Cao, Jian-Ping Yang, Peng-Fei Gao, Xiang Wang, Zhe Xu, Hui-Yun Weng, Yuan-Yuan Shang, Peng J Exp Clin Cancer Res Research BACKGROUND: CD147 plays a critical role in the invasive and metastatic activity of hepatocellular carcinoma (HCC) cells by stimulating the surrounding fibroblasts to express matrix metalloproteinases (MMPs). Tumor cells adhesion to extracellular matrix (ECM) proteins is the first step to the tumor metastasis. MMPs degrade the ECM to promote tumor metastasis. The aim of this study is to investigate the effects of small interfering RNA (siRNA) against CD147 (si-CD147) on hepatocellular carcinoma cells' (SMMC-7721) architecture and functions. METHODS: Flow cytometry and western blot assays were employed to detect the transfection efficiency of si-CD147. Confocal microscopy was used to determine the effects of si-CD147 on SMMC-7721 cells' cytoskeleton. Invasion assay, gelatin zymography and cell adhesion assay were employed to investigate the effects of si-CD147 on SMMC-7721 cells' invasion, gelatinase production and cell adhesive abilities. Western blot assay was utilized to detect the effects of si-CD147 on focal adhesion kinase (FAK), vinculiln and mitogen-activated protein kinase (MAPK) expression in SMMC-7721 cells. RESULTS: Downregulation of CD147 gene induced the alteration of SMMC-7721 cell cytoskeleton including actin, microtubule and vimentin filaments, and inhibited gelatinase production and expression, cells invasion, FAK and vinculin expression. si-CD147 also blocked SMMC-7721 cells adhesion to collagen IV and phosphorylation level of SAPK/JNKs. SAPK/JNKs inhibitor SP600125 inhibited gelatinase production and expression. CONCLUSION: CD147 is required for normal tumor cell architecture and cell invasion. Downregulation of CD147 affects HCC cell structure and function. Moreover, the alteration of cell behavior may be related to SAPK/JNK Pathway. siRNA against CD147 may be a possible new approach for HCC gene therapy. BioMed Central 2008-10-11 /pmc/articles/PMC2572039/ /pubmed/18847500 http://dx.doi.org/10.1186/1756-9966-27-50 Text en Copyright © 2008 Qian et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Qian, Ai-Rong
Zhang, Wei
Cao, Jian-Ping
Yang, Peng-Fei
Gao, Xiang
Wang, Zhe
Xu, Hui-Yun
Weng, Yuan-Yuan
Shang, Peng
Downregulation of CD147 expression alters cytoskeleton architecture and inhibits gelatinase production and SAPK pathway in human hepatocellular carcinoma cells
title Downregulation of CD147 expression alters cytoskeleton architecture and inhibits gelatinase production and SAPK pathway in human hepatocellular carcinoma cells
title_full Downregulation of CD147 expression alters cytoskeleton architecture and inhibits gelatinase production and SAPK pathway in human hepatocellular carcinoma cells
title_fullStr Downregulation of CD147 expression alters cytoskeleton architecture and inhibits gelatinase production and SAPK pathway in human hepatocellular carcinoma cells
title_full_unstemmed Downregulation of CD147 expression alters cytoskeleton architecture and inhibits gelatinase production and SAPK pathway in human hepatocellular carcinoma cells
title_short Downregulation of CD147 expression alters cytoskeleton architecture and inhibits gelatinase production and SAPK pathway in human hepatocellular carcinoma cells
title_sort downregulation of cd147 expression alters cytoskeleton architecture and inhibits gelatinase production and sapk pathway in human hepatocellular carcinoma cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2572039/
https://www.ncbi.nlm.nih.gov/pubmed/18847500
http://dx.doi.org/10.1186/1756-9966-27-50
work_keys_str_mv AT qianairong downregulationofcd147expressionalterscytoskeletonarchitectureandinhibitsgelatinaseproductionandsapkpathwayinhumanhepatocellularcarcinomacells
AT zhangwei downregulationofcd147expressionalterscytoskeletonarchitectureandinhibitsgelatinaseproductionandsapkpathwayinhumanhepatocellularcarcinomacells
AT caojianping downregulationofcd147expressionalterscytoskeletonarchitectureandinhibitsgelatinaseproductionandsapkpathwayinhumanhepatocellularcarcinomacells
AT yangpengfei downregulationofcd147expressionalterscytoskeletonarchitectureandinhibitsgelatinaseproductionandsapkpathwayinhumanhepatocellularcarcinomacells
AT gaoxiang downregulationofcd147expressionalterscytoskeletonarchitectureandinhibitsgelatinaseproductionandsapkpathwayinhumanhepatocellularcarcinomacells
AT wangzhe downregulationofcd147expressionalterscytoskeletonarchitectureandinhibitsgelatinaseproductionandsapkpathwayinhumanhepatocellularcarcinomacells
AT xuhuiyun downregulationofcd147expressionalterscytoskeletonarchitectureandinhibitsgelatinaseproductionandsapkpathwayinhumanhepatocellularcarcinomacells
AT wengyuanyuan downregulationofcd147expressionalterscytoskeletonarchitectureandinhibitsgelatinaseproductionandsapkpathwayinhumanhepatocellularcarcinomacells
AT shangpeng downregulationofcd147expressionalterscytoskeletonarchitectureandinhibitsgelatinaseproductionandsapkpathwayinhumanhepatocellularcarcinomacells