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Low Level of Low-Density Lipoprotein Receptor-Related Protein 1 Predicts an Unfavorable Prognosis of Hepatocellular Carcinoma after Curative Resection

BACKGROUND: Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional receptor involved in receptor-mediated endocytosis and cell signaling. The aim of this study was to elucidate the expression and mechanism of LRP1 in hepatocellular carcinoma (HCC). METHODS: LRP1 expression in...

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Autores principales: Huang, Xiao-Yong, Shi, Guo-Ming, Devbhandari, Ranjan Prasad, Ke, Ai-Wu, Wang, Yuwei, Wang, Xiao-Ying, Wang, Zheng, Shi, Ying-Hong, Xiao, Yong-Sheng, Ding, Zhen-Bin, Dai, Zhi, Xu, Yang, Jia, Wei-Ping, Tang, Zhao-You, Fan, Jia, Zhou, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299691/
https://www.ncbi.nlm.nih.gov/pubmed/22427881
http://dx.doi.org/10.1371/journal.pone.0032775
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author Huang, Xiao-Yong
Shi, Guo-Ming
Devbhandari, Ranjan Prasad
Ke, Ai-Wu
Wang, Yuwei
Wang, Xiao-Ying
Wang, Zheng
Shi, Ying-Hong
Xiao, Yong-Sheng
Ding, Zhen-Bin
Dai, Zhi
Xu, Yang
Jia, Wei-Ping
Tang, Zhao-You
Fan, Jia
Zhou, Jian
author_facet Huang, Xiao-Yong
Shi, Guo-Ming
Devbhandari, Ranjan Prasad
Ke, Ai-Wu
Wang, Yuwei
Wang, Xiao-Ying
Wang, Zheng
Shi, Ying-Hong
Xiao, Yong-Sheng
Ding, Zhen-Bin
Dai, Zhi
Xu, Yang
Jia, Wei-Ping
Tang, Zhao-You
Fan, Jia
Zhou, Jian
author_sort Huang, Xiao-Yong
collection PubMed
description BACKGROUND: Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional receptor involved in receptor-mediated endocytosis and cell signaling. The aim of this study was to elucidate the expression and mechanism of LRP1 in hepatocellular carcinoma (HCC). METHODS: LRP1 expression in 4 HCC cell lines and 40 HCC samples was detected. After interruption of LRP1 expression in a HCC cell line either with specific lentiviral-mediated shRNA LRP1 or in the presence of the LRP1-specific chaperone, receptor-associated protein (RAP), the role of LRP1 in the migration and invasion of HCC cells was assessed in vivo and in vitro, and the expression of matrix metalloproteinase (MMP) 9 in cells and the bioactivity of MMP9 in the supernatant were assayed. The expression and prognostic value of LRP1 were investigated in 327 HCC specimens. RESULTS: Low LRP1 expression was associated with poor HCC prognosis, with low expression independently related to shortened overall survival and increased tumor recurrence rate. Expression of LRP1 in non-recurrent HCC samples was significantly higher than that in early recurrent samples. LRP1 expression in HCC cell lines was inversely correlated with their metastatic potential. After inhibition of LRP1, low-metastatic SMCC-7721 cells showed enhanced migration and invasion and increased expression and bioactivity of MMP9. Correlation analysis showed a negative correlation between LRP1 and MMP9 expression in HCC patients. The prognostic value of LRP1 expression was validated in the independent data set. CONCLUSIONS: LRP1 modulated the level of MMP9 and low level of LRP1 expression was associated with aggressiveness and invasiveness in HCCs. LRP1 offered a possible strategy for tumor molecular therapy.
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spelling pubmed-32996912012-03-16 Low Level of Low-Density Lipoprotein Receptor-Related Protein 1 Predicts an Unfavorable Prognosis of Hepatocellular Carcinoma after Curative Resection Huang, Xiao-Yong Shi, Guo-Ming Devbhandari, Ranjan Prasad Ke, Ai-Wu Wang, Yuwei Wang, Xiao-Ying Wang, Zheng Shi, Ying-Hong Xiao, Yong-Sheng Ding, Zhen-Bin Dai, Zhi Xu, Yang Jia, Wei-Ping Tang, Zhao-You Fan, Jia Zhou, Jian PLoS One Research Article BACKGROUND: Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional receptor involved in receptor-mediated endocytosis and cell signaling. The aim of this study was to elucidate the expression and mechanism of LRP1 in hepatocellular carcinoma (HCC). METHODS: LRP1 expression in 4 HCC cell lines and 40 HCC samples was detected. After interruption of LRP1 expression in a HCC cell line either with specific lentiviral-mediated shRNA LRP1 or in the presence of the LRP1-specific chaperone, receptor-associated protein (RAP), the role of LRP1 in the migration and invasion of HCC cells was assessed in vivo and in vitro, and the expression of matrix metalloproteinase (MMP) 9 in cells and the bioactivity of MMP9 in the supernatant were assayed. The expression and prognostic value of LRP1 were investigated in 327 HCC specimens. RESULTS: Low LRP1 expression was associated with poor HCC prognosis, with low expression independently related to shortened overall survival and increased tumor recurrence rate. Expression of LRP1 in non-recurrent HCC samples was significantly higher than that in early recurrent samples. LRP1 expression in HCC cell lines was inversely correlated with their metastatic potential. After inhibition of LRP1, low-metastatic SMCC-7721 cells showed enhanced migration and invasion and increased expression and bioactivity of MMP9. Correlation analysis showed a negative correlation between LRP1 and MMP9 expression in HCC patients. The prognostic value of LRP1 expression was validated in the independent data set. CONCLUSIONS: LRP1 modulated the level of MMP9 and low level of LRP1 expression was associated with aggressiveness and invasiveness in HCCs. LRP1 offered a possible strategy for tumor molecular therapy. Public Library of Science 2012-03-12 /pmc/articles/PMC3299691/ /pubmed/22427881 http://dx.doi.org/10.1371/journal.pone.0032775 Text en Huang et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Huang, Xiao-Yong
Shi, Guo-Ming
Devbhandari, Ranjan Prasad
Ke, Ai-Wu
Wang, Yuwei
Wang, Xiao-Ying
Wang, Zheng
Shi, Ying-Hong
Xiao, Yong-Sheng
Ding, Zhen-Bin
Dai, Zhi
Xu, Yang
Jia, Wei-Ping
Tang, Zhao-You
Fan, Jia
Zhou, Jian
Low Level of Low-Density Lipoprotein Receptor-Related Protein 1 Predicts an Unfavorable Prognosis of Hepatocellular Carcinoma after Curative Resection
title Low Level of Low-Density Lipoprotein Receptor-Related Protein 1 Predicts an Unfavorable Prognosis of Hepatocellular Carcinoma after Curative Resection
title_full Low Level of Low-Density Lipoprotein Receptor-Related Protein 1 Predicts an Unfavorable Prognosis of Hepatocellular Carcinoma after Curative Resection
title_fullStr Low Level of Low-Density Lipoprotein Receptor-Related Protein 1 Predicts an Unfavorable Prognosis of Hepatocellular Carcinoma after Curative Resection
title_full_unstemmed Low Level of Low-Density Lipoprotein Receptor-Related Protein 1 Predicts an Unfavorable Prognosis of Hepatocellular Carcinoma after Curative Resection
title_short Low Level of Low-Density Lipoprotein Receptor-Related Protein 1 Predicts an Unfavorable Prognosis of Hepatocellular Carcinoma after Curative Resection
title_sort low level of low-density lipoprotein receptor-related protein 1 predicts an unfavorable prognosis of hepatocellular carcinoma after curative resection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299691/
https://www.ncbi.nlm.nih.gov/pubmed/22427881
http://dx.doi.org/10.1371/journal.pone.0032775
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