Annexin A2 promotes the migration and invasion of human hepatocellular carcinoma cells in vitro by regulating the shedding of CD147-harboring microvesicles from tumor cells

It has been reported that Annexin A2 (ANXA2) is up-regulated in hepatocellular carcinoma (HCC), but the roles of ANXA2 in the migration and invasion of HCC cells have not been determined. In this study, we found that ANXA2-specific siRNA (si-ANXA2) significantly inhibited the migration and invasion...

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Veröffentlicht in:PloS one 2013-08, Vol.8 (8), p.e67268-e67268
Hauptverfasser: Zhang, Wei, Zhao, Pu, Xu, Xiu-Li, Cai, Lei, Song, Zhen-Shun, Cao, Da-Yong, Tao, Kai-Shan, Zhou, Wen-Ping, Chen, Zhi-Nan, Dou, Ke-Feng
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container_title PloS one
container_volume 8
creator Zhang, Wei
Zhao, Pu
Xu, Xiu-Li
Cai, Lei
Song, Zhen-Shun
Cao, Da-Yong
Tao, Kai-Shan
Zhou, Wen-Ping
Chen, Zhi-Nan
Dou, Ke-Feng
description It has been reported that Annexin A2 (ANXA2) is up-regulated in hepatocellular carcinoma (HCC), but the roles of ANXA2 in the migration and invasion of HCC cells have not been determined. In this study, we found that ANXA2-specific siRNA (si-ANXA2) significantly inhibited the migration and invasion of HCC cells co-cultured with fibroblasts in vitro. In addition, the production of MMP-2 by fibroblasts cultured in supernatant collected from si-ANXA2-transfected HCC cells was notably down-regulated. ANXA2 was also found to be co-localized and co-immunoprecipitated with CD147. Further investigation revealed that the expression of ANXA2 in HCC cells affected the shedding of CD147-harboring membrane microvesicles, acting as a vehicle for CD147 in tumor-stromal interactions and thereby regulating the production of MMP-2 by fibroblasts. Together, these results suggest that ANXA2 enhances the migration and invasion potential of HCC cells in vitro by regulating the trafficking of CD147-harboring membrane microvesicles.
doi_str_mv 10.1371/journal.pone.0067268
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In this study, we found that ANXA2-specific siRNA (si-ANXA2) significantly inhibited the migration and invasion of HCC cells co-cultured with fibroblasts in vitro. In addition, the production of MMP-2 by fibroblasts cultured in supernatant collected from si-ANXA2-transfected HCC cells was notably down-regulated. ANXA2 was also found to be co-localized and co-immunoprecipitated with CD147. Further investigation revealed that the expression of ANXA2 in HCC cells affected the shedding of CD147-harboring membrane microvesicles, acting as a vehicle for CD147 in tumor-stromal interactions and thereby regulating the production of MMP-2 by fibroblasts. Together, these results suggest that ANXA2 enhances the migration and invasion potential of HCC cells in vitro by regulating the trafficking of CD147-harboring membrane microvesicles.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23950866</pmid><doi>10.1371/journal.pone.0067268</doi><tpages>e67268</tpages><oa>free_for_read</oa></addata></record>
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subjects Angiogenesis
Annexin A2 - genetics
Annexin A2 - metabolism
Annexins
Basigin - metabolism
Binding sites
Biology
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - pathology
CD147 antigen
Cell Line, Tumor
Cell Membrane - metabolism
Cell Movement - genetics
Chemistry
Coculture Techniques
Engineering research
Extracellular matrix
Fibroblasts
Gelatinase A
Gene Expression Regulation, Neoplastic
Hepatocellular carcinoma
Humans
Immunoglobulins
Kinases
Laboratories
Liver cancer
Liver Neoplasms - genetics
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Medicine
Membrane trafficking
Metastasis
Microvessels - metabolism
Microvessels - pathology
Neoplasm Invasiveness
Neovascularization, Pathologic - genetics
Neovascularization, Pathologic - metabolism
Prostate cancer
Protein Binding
Protein Transport
Proteins
RNA Interference
Shedding
Signal transduction
siRNA
Surgery
Tumor cells
Tumors
title Annexin A2 promotes the migration and invasion of human hepatocellular carcinoma cells in vitro by regulating the shedding of CD147-harboring microvesicles from tumor cells
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