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Full-length soluble CD147 promotes MMP-2 expression and is a potential serological marker in detection of hepatocellular carcinoma

As a surface glycoprotein, CD147 is capable of stimulating the production of matrix metalloproteinases (MMPs) from neighboring fibroblasts. The aim of the present study is to explore the role of soluble CD147 on MMPs secretion from hepatocellular carcinoma (HCC) cells, and to investigate the diagnos...

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Published in:Journal of translational medicine 2014-07, Vol.12 (1), p.190-190, Article 190
Main Authors: Wu, Jiao, Hao, Zhi-Wei, Zhao, You-Xu, Yang, Xiang-Min, Tang, Hao, Zhang, Xin, Song, Fei, Sun, Xiu-Xuan, Wang, Bin, Nan, Gang, Chen, Zhi-Nan, Bian, Huijie
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container_title Journal of translational medicine
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creator Wu, Jiao
Hao, Zhi-Wei
Zhao, You-Xu
Yang, Xiang-Min
Tang, Hao
Zhang, Xin
Song, Fei
Sun, Xiu-Xuan
Wang, Bin
Nan, Gang
Chen, Zhi-Nan
Bian, Huijie
description As a surface glycoprotein, CD147 is capable of stimulating the production of matrix metalloproteinases (MMPs) from neighboring fibroblasts. The aim of the present study is to explore the role of soluble CD147 on MMPs secretion from hepatocellular carcinoma (HCC) cells, and to investigate the diagnostic value of serum soluble CD147 in the HCC detection. We identified the form of soluble CD147 in cell culture supernate of HCC cells and serum of patients with HCC, and explored the role of soluble CD147 on MMPs secretion. Serum CD147 levels were detected by the enzyme-linked immunosorbent assay, and the value of soluble CD147 as a marker in HCC detection was analyzed. Full length soluble CD147 was presented in the culture medium of HCC cells and serum of patients with HCC. The extracellular domain of soluble CD147 promoted the expression of CD147 and MMP-2 from HCC cells. Knockdown of CD147 markedly diminished the up-regulation of CD147 and MMP-2 which induced by soluble CD147. Soluble CD147 activated ERK, FAK, and PI3K/Akt pathways, leading to the up-regulation of MMP-2. The level of soluble CD147 in serum of patients with HCC was significantly elevated compared with healthy individuals (P 
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The aim of the present study is to explore the role of soluble CD147 on MMPs secretion from hepatocellular carcinoma (HCC) cells, and to investigate the diagnostic value of serum soluble CD147 in the HCC detection. We identified the form of soluble CD147 in cell culture supernate of HCC cells and serum of patients with HCC, and explored the role of soluble CD147 on MMPs secretion. Serum CD147 levels were detected by the enzyme-linked immunosorbent assay, and the value of soluble CD147 as a marker in HCC detection was analyzed. Full length soluble CD147 was presented in the culture medium of HCC cells and serum of patients with HCC. The extracellular domain of soluble CD147 promoted the expression of CD147 and MMP-2 from HCC cells. Knockdown of CD147 markedly diminished the up-regulation of CD147 and MMP-2 which induced by soluble CD147. Soluble CD147 activated ERK, FAK, and PI3K/Akt pathways, leading to the up-regulation of MMP-2. The level of soluble CD147 in serum of patients with HCC was significantly elevated compared with healthy individuals (P &lt; 0.001). Soluble CD147 levels were found to be associated with HCC tumor size (P = 0.007) and Child-Pugh grade (P = 0.007). Moreover, soluble CD147 showed a better performance in distinguishing HCC compared with alpha-fetoprotein. The extracellular domain of soluble CD147 enhances the secretion of MMP-2 from HCC cells, requiring the cooperation of membrane CD147 and activation of ERK, FAK, and PI3K/Akt signaling. 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This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</rights><rights>Copyright © 2014 Wu et al.; licensee BioMed Central Ltd. 2014 Wu et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b617t-c54205625f7d48effc095b65d3dfae52da3528197b32da694dae8066eb2886873</citedby><cites>FETCH-LOGICAL-b617t-c54205625f7d48effc095b65d3dfae52da3528197b32da694dae8066eb2886873</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227008/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1553442870?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24996644$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Jiao</creatorcontrib><creatorcontrib>Hao, Zhi-Wei</creatorcontrib><creatorcontrib>Zhao, You-Xu</creatorcontrib><creatorcontrib>Yang, Xiang-Min</creatorcontrib><creatorcontrib>Tang, Hao</creatorcontrib><creatorcontrib>Zhang, Xin</creatorcontrib><creatorcontrib>Song, Fei</creatorcontrib><creatorcontrib>Sun, Xiu-Xuan</creatorcontrib><creatorcontrib>Wang, Bin</creatorcontrib><creatorcontrib>Nan, Gang</creatorcontrib><creatorcontrib>Chen, Zhi-Nan</creatorcontrib><creatorcontrib>Bian, Huijie</creatorcontrib><title>Full-length soluble CD147 promotes MMP-2 expression and is a potential serological marker in detection of hepatocellular carcinoma</title><title>Journal of translational medicine</title><addtitle>J Transl Med</addtitle><description>As a surface glycoprotein, CD147 is capable of stimulating the production of matrix metalloproteinases (MMPs) from neighboring fibroblasts. 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The aim of the present study is to explore the role of soluble CD147 on MMPs secretion from hepatocellular carcinoma (HCC) cells, and to investigate the diagnostic value of serum soluble CD147 in the HCC detection. We identified the form of soluble CD147 in cell culture supernate of HCC cells and serum of patients with HCC, and explored the role of soluble CD147 on MMPs secretion. Serum CD147 levels were detected by the enzyme-linked immunosorbent assay, and the value of soluble CD147 as a marker in HCC detection was analyzed. Full length soluble CD147 was presented in the culture medium of HCC cells and serum of patients with HCC. The extracellular domain of soluble CD147 promoted the expression of CD147 and MMP-2 from HCC cells. Knockdown of CD147 markedly diminished the up-regulation of CD147 and MMP-2 which induced by soluble CD147. Soluble CD147 activated ERK, FAK, and PI3K/Akt pathways, leading to the up-regulation of MMP-2. The level of soluble CD147 in serum of patients with HCC was significantly elevated compared with healthy individuals (P &lt; 0.001). Soluble CD147 levels were found to be associated with HCC tumor size (P = 0.007) and Child-Pugh grade (P = 0.007). Moreover, soluble CD147 showed a better performance in distinguishing HCC compared with alpha-fetoprotein. The extracellular domain of soluble CD147 enhances the secretion of MMP-2 from HCC cells, requiring the cooperation of membrane CD147 and activation of ERK, FAK, and PI3K/Akt signaling. The measurement of soluble CD147 may offer a useful approach in diagnosis of HCC.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>24996644</pmid><doi>10.1186/1479-5876-12-190</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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subjects Adult
Aged
alpha-Fetoproteins - metabolism
Basigin - blood
Basigin - chemistry
Basigin - metabolism
Biology
Biomarkers, Tumor - blood
Biotechnology
Carcinoma, Hepatocellular - blood
Carcinoma, Hepatocellular - diagnosis
Carcinoma, Hepatocellular - enzymology
Carcinoma, Hepatocellular - pathology
Case-Control Studies
Cell Line, Tumor
Cell Membrane - metabolism
Culture Media, Conditioned - metabolism
Diagnosis
Enzyme-linked immunosorbent assay
Enzymes
Extracellular Signal-Regulated MAP Kinases - metabolism
Female
Focal Adhesion Protein-Tyrosine Kinases - metabolism
Genetic aspects
Hepatoma
Humans
Life sciences
Liver cancer
Liver Neoplasms - blood
Liver Neoplasms - diagnosis
Liver Neoplasms - enzymology
Liver Neoplasms - pathology
Male
Matrix Metalloproteinase 2 - metabolism
Matrix Metalloproteinase 2 - secretion
Metastasis
Middle Aged
Neoplasm Staging
Phosphatidylinositol 3-Kinases - metabolism
Physiological aspects
Protein Binding
Protein Structure, Tertiary
Proteins
Proto-Oncogene Proteins c-akt - metabolism
ROC Curve
Signal Transduction
Solubility
Up-Regulation
title Full-length soluble CD147 promotes MMP-2 expression and is a potential serological marker in detection of hepatocellular carcinoma
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