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Conference Paper: The Molecular Mechanisms of the Dual Anti-Angiogenic and Anti-Tumor Effects of rAAV-HGFK1

TitleThe Molecular Mechanisms of the Dual Anti-Angiogenic and Anti-Tumor Effects of rAAV-HGFK1
Authors
Issue Date2008
PublisherNature Publishing Group
Citation
The 11th Annual Meeting of the American Society of Gene Therapy, Boston, MA, 28 May-1 June 2008. In Molecular Therapy, 2008, v. 16 n. S1, p. S228 Abstract no. 611 How to Cite?
AbstractThe kringle 1 domain of human hepatocyte growth factor (HGFK1) was previously shown to inhibit bovine aortic endothelial (BAE) cell proliferation, suggesting that it might be an anti-angiogenic molecule. Recently, we demonstrated the in vivo efficacy of a recombinant adeno-associated virus carrying HGFK1 (rAAV-HGFK1) for the treatment of hepatocellular carcinoma (HCC) in a rat orthotopic HCC model. We showed that HGFK1 exhibited dual anti-angiogenic and anti-tumor cell effects on hepatocellular carcinoma. To our surprise, HGFK1 did not act through the HGF/HGFR pathway. Instead, it worked mainly through EGF/EGFR signaling, with more minor contributions from VEGF/VEGFR and bFGF/bFGFR signaling in both MECs and tumor cells. To understand the molecular mechanisms and down-stream targets of rAAV-HGFK1, we applied genome-wide expression profiling technology followed by RT-PCR validation, to examine the differentially expressed genes upon rAAV-HGFK1 treatment on mice microvessel endothelial cells (MECs) and rat hepatoma McA-RH7777 cell lines, as compared with rAAV-EGFP (Enhanced green fluorescent protein) treatment. Our results showed that three groups of mechanisms were involved in the anti-angiogenic and anti-tumor signaling network of rAAV-HGFK1: (1) Promotion of apoptosis, (2) Promotion of JNK signaling cascade, and (3) Promotion of cell adhesion and cell migration. In conclusion, this study reveals the pathways regulated by rAAV-HGFK1 and contributes to the further development of HGFK1 cancer gene therapy for the treatment of hepatocellular carcinoma (HCC).
Persistent Identifierhttp://hdl.handle.net/10722/97044
ISSN
2015 Impact Factor: 6.938
2015 SCImago Journal Rankings: 3.374

 

DC FieldValueLanguage
dc.contributor.authorShen, Zen_HK
dc.contributor.authorLeung, WSen_HK
dc.contributor.authorYiu, SMen_HK
dc.contributor.authorKung, HFen_HK
dc.contributor.authorLin, MCen_HK
dc.date.accessioned2010-09-25T16:54:24Z-
dc.date.available2010-09-25T16:54:24Z-
dc.date.issued2008en_HK
dc.identifier.citationThe 11th Annual Meeting of the American Society of Gene Therapy, Boston, MA, 28 May-1 June 2008. In Molecular Therapy, 2008, v. 16 n. S1, p. S228 Abstract no. 611-
dc.identifier.issn1525-0016-
dc.identifier.urihttp://hdl.handle.net/10722/97044-
dc.description.abstractThe kringle 1 domain of human hepatocyte growth factor (HGFK1) was previously shown to inhibit bovine aortic endothelial (BAE) cell proliferation, suggesting that it might be an anti-angiogenic molecule. Recently, we demonstrated the in vivo efficacy of a recombinant adeno-associated virus carrying HGFK1 (rAAV-HGFK1) for the treatment of hepatocellular carcinoma (HCC) in a rat orthotopic HCC model. We showed that HGFK1 exhibited dual anti-angiogenic and anti-tumor cell effects on hepatocellular carcinoma. To our surprise, HGFK1 did not act through the HGF/HGFR pathway. Instead, it worked mainly through EGF/EGFR signaling, with more minor contributions from VEGF/VEGFR and bFGF/bFGFR signaling in both MECs and tumor cells. To understand the molecular mechanisms and down-stream targets of rAAV-HGFK1, we applied genome-wide expression profiling technology followed by RT-PCR validation, to examine the differentially expressed genes upon rAAV-HGFK1 treatment on mice microvessel endothelial cells (MECs) and rat hepatoma McA-RH7777 cell lines, as compared with rAAV-EGFP (Enhanced green fluorescent protein) treatment. Our results showed that three groups of mechanisms were involved in the anti-angiogenic and anti-tumor signaling network of rAAV-HGFK1: (1) Promotion of apoptosis, (2) Promotion of JNK signaling cascade, and (3) Promotion of cell adhesion and cell migration. In conclusion, this study reveals the pathways regulated by rAAV-HGFK1 and contributes to the further development of HGFK1 cancer gene therapy for the treatment of hepatocellular carcinoma (HCC).-
dc.languageengen_HK
dc.publisherNature Publishing Group-
dc.relation.ispartofMolecular Therapyen_HK
dc.titleThe Molecular Mechanisms of the Dual Anti-Angiogenic and Anti-Tumor Effects of rAAV-HGFK1en_HK
dc.typeConference_Paperen_HK
dc.identifier.emailYiu, SM: smyiu@cs.hku.hken_HK
dc.identifier.emailLin, MC: mcllin@HKUCC.hku.hken_HK
dc.identifier.authorityYiu, SM=rp00207en_HK
dc.identifier.authorityLin, MC=rp00746en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/S1525-0016(16)40014-6-
dc.identifier.hkuros139940en_HK

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