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Article: Suppression of liver tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of rho kinase/IFN-inducible protein 10/matrix metalloproteinase 9 signaling

TitleSuppression of liver tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of rho kinase/IFN-inducible protein 10/matrix metalloproteinase 9 signaling
Authors
Issue Date2010
PublisherAmerican Association for Cancer Research.
Citation
Clinical Cancer Research, 2010, v. 16 n. 3, p. 967-977 How to Cite?
AbstractPurpose: We aimed to investigate the effects of adiponectin on liver cancer growth and metastasis and explore the underlying mechanisms. Experimental Design: An orthotopic liver tumor nude mice model with distant metastatic potential was applied. Either Ad-adiponectin (1 × 10 8; treatment group) or Ad-luciferase (control group) was injected via portal vein after tumor implantation. Tumor growth and metastasis were monitored by Xenogen In vivo Imaging System. Hepatic stellate cell activation by α-smooth muscle actin staining, microvessel density by CD34 staining, macrophage infiltration in tumor tissue, and cell signaling leading to invasion, migration [Rho kinase (ROCK), IFN-inducible protein 10 (IP10), and matrix metalloproteinase 9], and angiogenesis [vascular endothelial growth factor (VEGF) and angiopoietin 1] were also compared. Tumor-nontumor margin was examined under electron microscopy. Direct effects of adiponectin on liver cancer cells and endothelial cells were further investigated by a series of functional studies. Results: Tumor growth was significantly inhibited by adiponectin treatment, accompanied by a lower incidence of lung metastasis. Hepatic stellate cell activation and macrophage infiltration in the liver tumors were suppressed by adiponectin treatment, along with decreased microvessel density. The treatment group had less Ki-67-positive tumor cells and downregulated protein expression of ROCK1, proline-rich tyrosine kinase 2, and VEGF. Tumor vascular endothelial cell damage was found in the treatment group under electron microscopy. In vitro functional study showed that adiponectin not only downregulated the ROCK/IP10/VEGF signaling pathway but also inhibited the formation of lamellipodia, which contribute to cell migration. Conclusion: Adiponectin treatment significantly inhibited liver tumor growth and metastasis by suppression of tumor angiogenesis and downregulation of the ROCK/IP10/matrix metalloproteinase 9 pathway. ©2010 AACR.
Persistent Identifierhttp://hdl.handle.net/10722/73589
ISSN
2015 Impact Factor: 8.738
2015 SCImago Journal Rankings: 5.314
ISI Accession Number ID
Funding AgencyGrant Number
University of Hong Kong
RGCHKU5/CRF/08
Funding Information:

Seed Funding Programme for Basic Research, University of Hong Kong and in part by the RGC Collaborative Research Fund (Ref. No. HKU5/CRF/08).

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorMan, Ken_HK
dc.contributor.authorNg, KTPen_HK
dc.contributor.authorXu, Aen_HK
dc.contributor.authorCheng, Qen_HK
dc.contributor.authorLo, CMen_HK
dc.contributor.authorXiao, JWen_HK
dc.contributor.authorSun, BSen_HK
dc.contributor.authorLim, ZXHen_HK
dc.contributor.authorCheung, JSen_HK
dc.contributor.authorWu, EXen_HK
dc.contributor.authorSun, CKWen_HK
dc.contributor.authorPoon, RTPen_HK
dc.contributor.authorFan, STen_HK
dc.date.accessioned2010-09-06T06:52:50Z-
dc.date.available2010-09-06T06:52:50Z-
dc.date.issued2010en_HK
dc.identifier.citationClinical Cancer Research, 2010, v. 16 n. 3, p. 967-977en_HK
dc.identifier.issn1078-0432en_HK
dc.identifier.urihttp://hdl.handle.net/10722/73589-
dc.description.abstractPurpose: We aimed to investigate the effects of adiponectin on liver cancer growth and metastasis and explore the underlying mechanisms. Experimental Design: An orthotopic liver tumor nude mice model with distant metastatic potential was applied. Either Ad-adiponectin (1 × 10 8; treatment group) or Ad-luciferase (control group) was injected via portal vein after tumor implantation. Tumor growth and metastasis were monitored by Xenogen In vivo Imaging System. Hepatic stellate cell activation by α-smooth muscle actin staining, microvessel density by CD34 staining, macrophage infiltration in tumor tissue, and cell signaling leading to invasion, migration [Rho kinase (ROCK), IFN-inducible protein 10 (IP10), and matrix metalloproteinase 9], and angiogenesis [vascular endothelial growth factor (VEGF) and angiopoietin 1] were also compared. Tumor-nontumor margin was examined under electron microscopy. Direct effects of adiponectin on liver cancer cells and endothelial cells were further investigated by a series of functional studies. Results: Tumor growth was significantly inhibited by adiponectin treatment, accompanied by a lower incidence of lung metastasis. Hepatic stellate cell activation and macrophage infiltration in the liver tumors were suppressed by adiponectin treatment, along with decreased microvessel density. The treatment group had less Ki-67-positive tumor cells and downregulated protein expression of ROCK1, proline-rich tyrosine kinase 2, and VEGF. Tumor vascular endothelial cell damage was found in the treatment group under electron microscopy. In vitro functional study showed that adiponectin not only downregulated the ROCK/IP10/VEGF signaling pathway but also inhibited the formation of lamellipodia, which contribute to cell migration. Conclusion: Adiponectin treatment significantly inhibited liver tumor growth and metastasis by suppression of tumor angiogenesis and downregulation of the ROCK/IP10/matrix metalloproteinase 9 pathway. ©2010 AACR.en_HK
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research.en_HK
dc.relation.ispartofClinical Cancer Researchen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshCarcinoma, Hepatocellular - blood supply - drug therapy - pathology-
dc.subject.meshChemokine CXCL10 - metabolism-
dc.subject.meshLiver Neoplasms, Experimental - blood supply - drug therapy - pathology-
dc.subject.meshMatrix Metalloproteinase 9 - metabolism-
dc.subject.meshNeovascularization, Pathologic - drug therapy-
dc.titleSuppression of liver tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of rho kinase/IFN-inducible protein 10/matrix metalloproteinase 9 signalingen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1078-0432&volume=16&issue=3&spage=967&epage=977&date=2010&atitle=Suppression+of+liver+tumor+growth+and+metastasis+by+adiponectin+in+nude+mice+through+inhibition+of+tumor+angiogenesis+and+downregulation+of+Rho+kinase/IFN-inducible+protein+10/matrix+metalloproteinase+9+signalingen_HK
dc.identifier.emailMan, K: kwanman@hku.hken_HK
dc.identifier.emailNg, KTP: ledodes@hku.hken_HK
dc.identifier.emailXu, A: amxu@hkucc.hku.hken_HK
dc.identifier.emailLo, CM: chungmlo@hkucc.hku.hken_HK
dc.identifier.emailWu, EX: ewu1@hkucc.hku.hken_HK
dc.identifier.emailPoon, RTP: poontp@hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityMan, K=rp00417en_HK
dc.identifier.authorityNg, KTP=rp01720en_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.identifier.authorityLo, CM=rp00412en_HK
dc.identifier.authorityWu, EX=rp00193en_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.description.naturepostprint-
dc.identifier.doi10.1158/1078-0432.CCR-09-1487en_HK
dc.identifier.pmid20103676-
dc.identifier.scopuseid_2-s2.0-76049087581en_HK
dc.identifier.hkuros169112en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-76049087581&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume16en_HK
dc.identifier.issue3en_HK
dc.identifier.spage967en_HK
dc.identifier.epage977en_HK
dc.identifier.eissn1078-0432-
dc.identifier.isiWOS:000278545100020-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectLiver Transplantation Research Centre: A Multidisciplinary Study for Liver Graft Injury-
dc.identifier.scopusauthoridMan, K=7101754072en_HK
dc.identifier.scopusauthoridNg, KTP=7403178513en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK
dc.identifier.scopusauthoridCheng, Q=16024087700en_HK
dc.identifier.scopusauthoridLo, CM=7401771672en_HK
dc.identifier.scopusauthoridXiao, JW=24336664800en_HK
dc.identifier.scopusauthoridSun, BS=23101636500en_HK
dc.identifier.scopusauthoridLim, ZXH=25822628500en_HK
dc.identifier.scopusauthoridCheung, JS=16174280400en_HK
dc.identifier.scopusauthoridWu, EX=7202128034en_HK
dc.identifier.scopusauthoridSun, CKW=7404248685en_HK
dc.identifier.scopusauthoridPoon, RTP=7103097223en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK

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