Neuropilin-1 promotes primary liver cancer progression by potentiating the activity of hepatic stellate cells

As a co-receptor for a variety of cytokines, neuropilin-1 (NRP-1) is detectable in primary liver cancer (PLC) cells. Previous studies determined that silencing of NRP-1 expression attenuated the proliferation, migration and invasion of PLC cells. An increasing number of studies have highlighted the...

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Veröffentlicht in:Oncology letters 2018-02, Vol.15 (2), p.2245-2251
Hauptverfasser: Xu, Zhi-Chao, Shen, Hao-Xin, Chen, Chen, Ma, Li, Li, Wen-Zhi, Wang, Lin, Geng, Zhi-Min
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container_issue 2
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container_title Oncology letters
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creator Xu, Zhi-Chao
Shen, Hao-Xin
Chen, Chen
Ma, Li
Li, Wen-Zhi
Wang, Lin
Geng, Zhi-Min
description As a co-receptor for a variety of cytokines, neuropilin-1 (NRP-1) is detectable in primary liver cancer (PLC) cells. Previous studies determined that silencing of NRP-1 expression attenuated the proliferation, migration and invasion of PLC cells. An increasing number of studies have highlighted the crucial role of the tumor microenvironment in the pathogenesis of cancer. Hepatic stellate cells (HSCs) are one of the major interstitial cell types present in the liver tumor microenvironment, and can promote the proliferation, migration and invasion of PLC cells. It remains unknown whether NRP-1 can promote PLC progression by potentiating the activity of HSCs. In the present study, the expression of NRP-1, and its co-expression with platelet-derived growth factor receptor-β, in HSCs was detected via immunofluorescence. LX2 HSCs were transfected with NRP-1 short hairpin RNA lentiviral vectors and their proliferation was observed. The proliferation, migration and invasion of HepG2 cells co-cultured with LX2 cells were also observed. Finally, LX2 and HepG2 cells were co-injected into nude mice as subcutaneous xenografts, and the tumor growth and α-smooth muscle actin expression levels were observed. NRP-1 knockdown attenuated LX2 cell activation, with concomitant downregulation of HepG2 cell proliferation, migration and invasion (P
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Previous studies determined that silencing of NRP-1 expression attenuated the proliferation, migration and invasion of PLC cells. An increasing number of studies have highlighted the crucial role of the tumor microenvironment in the pathogenesis of cancer. Hepatic stellate cells (HSCs) are one of the major interstitial cell types present in the liver tumor microenvironment, and can promote the proliferation, migration and invasion of PLC cells. It remains unknown whether NRP-1 can promote PLC progression by potentiating the activity of HSCs. In the present study, the expression of NRP-1, and its co-expression with platelet-derived growth factor receptor-β, in HSCs was detected via immunofluorescence. LX2 HSCs were transfected with NRP-1 short hairpin RNA lentiviral vectors and their proliferation was observed. The proliferation, migration and invasion of HepG2 cells co-cultured with LX2 cells were also observed. Finally, LX2 and HepG2 cells were co-injected into nude mice as subcutaneous xenografts, and the tumor growth and α-smooth muscle actin expression levels were observed. NRP-1 knockdown attenuated LX2 cell activation, with concomitant downregulation of HepG2 cell proliferation, migration and invasion (P&lt;0.05). Thus, silencing of NRP-1 expression may inhibit the activation of HSCs, as well as the proliferation, migration and invasion of PLC cells. The mechanism underlying the inhibition of PLC cell progression is possibly mediated by the inhibition of HSC activation, reduction of transforming growth factor-β1 levels in the conditioned medium and downregulation of extracellular signal-related kinase activity in PLC cells. Thus, NRP-1 could be regarded as a potential gene therapy target for PLC.</description><identifier>ISSN: 1792-1074</identifier><identifier>EISSN: 1792-1082</identifier><identifier>DOI: 10.3892/ol.2017.7541</identifier><identifier>PMID: 29434931</identifier><language>eng</language><publisher>Greece: Spandidos Publications</publisher><subject>Apoptosis ; Care and treatment ; Cytokines ; Development and progression ; Experiments ; Gene expression ; Genetic aspects ; Growth factors ; Health aspects ; Innovations ; Kinases ; Laboratory animals ; Liver cancer ; Metastasis ; Molecular targeted therapy ; Oncology ; Studies ; Tumors</subject><ispartof>Oncology letters, 2018-02, Vol.15 (2), p.2245-2251</ispartof><rights>COPYRIGHT 2018 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2018</rights><rights>Copyright: © Xu et al. 2018</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c443t-c6b937b0460b264b709afea08e7ae2e5b8e9af310eb7444c239e07c97eb47633</citedby><cites>FETCH-LOGICAL-c443t-c6b937b0460b264b709afea08e7ae2e5b8e9af310eb7444c239e07c97eb47633</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/PMC5777127/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777127/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29434931$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, Zhi-Chao</creatorcontrib><creatorcontrib>Shen, Hao-Xin</creatorcontrib><creatorcontrib>Chen, Chen</creatorcontrib><creatorcontrib>Ma, Li</creatorcontrib><creatorcontrib>Li, Wen-Zhi</creatorcontrib><creatorcontrib>Wang, Lin</creatorcontrib><creatorcontrib>Geng, Zhi-Min</creatorcontrib><title>Neuropilin-1 promotes primary liver cancer progression by potentiating the activity of hepatic stellate cells</title><title>Oncology letters</title><addtitle>Oncol Lett</addtitle><description>As a co-receptor for a variety of cytokines, neuropilin-1 (NRP-1) is detectable in primary liver cancer (PLC) cells. Previous studies determined that silencing of NRP-1 expression attenuated the proliferation, migration and invasion of PLC cells. An increasing number of studies have highlighted the crucial role of the tumor microenvironment in the pathogenesis of cancer. Hepatic stellate cells (HSCs) are one of the major interstitial cell types present in the liver tumor microenvironment, and can promote the proliferation, migration and invasion of PLC cells. It remains unknown whether NRP-1 can promote PLC progression by potentiating the activity of HSCs. In the present study, the expression of NRP-1, and its co-expression with platelet-derived growth factor receptor-β, in HSCs was detected via immunofluorescence. LX2 HSCs were transfected with NRP-1 short hairpin RNA lentiviral vectors and their proliferation was observed. The proliferation, migration and invasion of HepG2 cells co-cultured with LX2 cells were also observed. Finally, LX2 and HepG2 cells were co-injected into nude mice as subcutaneous xenografts, and the tumor growth and α-smooth muscle actin expression levels were observed. NRP-1 knockdown attenuated LX2 cell activation, with concomitant downregulation of HepG2 cell proliferation, migration and invasion (P&lt;0.05). Thus, silencing of NRP-1 expression may inhibit the activation of HSCs, as well as the proliferation, migration and invasion of PLC cells. The mechanism underlying the inhibition of PLC cell progression is possibly mediated by the inhibition of HSC activation, reduction of transforming growth factor-β1 levels in the conditioned medium and downregulation of extracellular signal-related kinase activity in PLC cells. 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Finally, LX2 and HepG2 cells were co-injected into nude mice as subcutaneous xenografts, and the tumor growth and α-smooth muscle actin expression levels were observed. NRP-1 knockdown attenuated LX2 cell activation, with concomitant downregulation of HepG2 cell proliferation, migration and invasion (P&lt;0.05). Thus, silencing of NRP-1 expression may inhibit the activation of HSCs, as well as the proliferation, migration and invasion of PLC cells. The mechanism underlying the inhibition of PLC cell progression is possibly mediated by the inhibition of HSC activation, reduction of transforming growth factor-β1 levels in the conditioned medium and downregulation of extracellular signal-related kinase activity in PLC cells. Thus, NRP-1 could be regarded as a potential gene therapy target for PLC.</abstract><cop>Greece</cop><pub>Spandidos Publications</pub><pmid>29434931</pmid><doi>10.3892/ol.2017.7541</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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subjects Apoptosis
Care and treatment
Cytokines
Development and progression
Experiments
Gene expression
Genetic aspects
Growth factors
Health aspects
Innovations
Kinases
Laboratory animals
Liver cancer
Metastasis
Molecular targeted therapy
Oncology
Studies
Tumors
title Neuropilin-1 promotes primary liver cancer progression by potentiating the activity of hepatic stellate cells
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