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Article: Vastatin, an Endogenous Antiangiogenesis Polypeptide That Is Lost in Hepatocellular Carcinoma, Effectively Inhibits Tumor Metastasis

TitleVastatin, an Endogenous Antiangiogenesis Polypeptide That Is Lost in Hepatocellular Carcinoma, Effectively Inhibits Tumor Metastasis
Authors
Issue Date2016
Citation
Molecular Therapy, 2016, v. 24, n. 8, p. 1358-1368 How to Cite?
AbstractHepatocellular carcinoma (HCC) is a hypervascular cancer without effective treatment. Here we report that polypeptide of NC1 domain of type VIII collagen (Vastatin) is an endogenous polypeptide expressed in normal liver tissue but lost in the liver of most HCC patients (73.1%). Its expression level is negatively associated with tumor size (P = 0.035) and metastasis (P = 0.016) in HCC patients. To evaluate its potential use as a therapeutic, we constructed a recombinant adeno-associated virus carrying Vastatin (rAAV-Vastatin) to treat HCC in an orthotopic Buffalo rat model. rAAV-Vastatin treatment significantly prolonged the median survival, inhibited tumor growth, and completely prevented metastasis in HCC-bearing rats by decreasing microvessel density and increasing tumor necrosis. No detectable toxicity in nontumor-bearing mice was observed. To investigate its molecular mechanisms, we performed DNA microarray, western blotting assays, and bioinformatic analysis to determine its effect on global gene expression patterns and signal transduction pathways. Our results indicated that rAAV-Vastatin significantly reduced the expressions of Pck1, JAG2, and c-Fos, thus inhibiting the cellular metabolism, Notch and AP-1 signaling pathways, respectively. Hence, we demonstrated for the first time that Vastatin is a novel, safe, and effective antiangiogenic therapeutic and a potential biomarker for HCC.
Persistent Identifierhttp://hdl.handle.net/10722/325327
ISSN
2023 Impact Factor: 12.1
2023 SCImago Journal Rankings: 3.736
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorShen, Zan-
dc.contributor.authorYao, Chen-
dc.contributor.authorWang, Zifeng-
dc.contributor.authorYue, Lu-
dc.contributor.authorFang, Zheping-
dc.contributor.authorYao, Hong-
dc.contributor.authorLin, Feng-
dc.contributor.authorZhao, Hui-
dc.contributor.authorSun, Yuan Jue-
dc.contributor.authorBian, Xiu Wu-
dc.contributor.authorJiang, Wenqi-
dc.contributor.authorWang, Xiaomei-
dc.contributor.authorLi, Yi-
dc.contributor.authorLu, Gang-
dc.contributor.authorPoon, Wai Sang-
dc.contributor.authorKung, Hsiang Fu-
dc.contributor.authorLin, Marie Chia Mi-
dc.date.accessioned2023-02-27T07:31:35Z-
dc.date.available2023-02-27T07:31:35Z-
dc.date.issued2016-
dc.identifier.citationMolecular Therapy, 2016, v. 24, n. 8, p. 1358-1368-
dc.identifier.issn1525-0016-
dc.identifier.urihttp://hdl.handle.net/10722/325327-
dc.description.abstractHepatocellular carcinoma (HCC) is a hypervascular cancer without effective treatment. Here we report that polypeptide of NC1 domain of type VIII collagen (Vastatin) is an endogenous polypeptide expressed in normal liver tissue but lost in the liver of most HCC patients (73.1%). Its expression level is negatively associated with tumor size (P = 0.035) and metastasis (P = 0.016) in HCC patients. To evaluate its potential use as a therapeutic, we constructed a recombinant adeno-associated virus carrying Vastatin (rAAV-Vastatin) to treat HCC in an orthotopic Buffalo rat model. rAAV-Vastatin treatment significantly prolonged the median survival, inhibited tumor growth, and completely prevented metastasis in HCC-bearing rats by decreasing microvessel density and increasing tumor necrosis. No detectable toxicity in nontumor-bearing mice was observed. To investigate its molecular mechanisms, we performed DNA microarray, western blotting assays, and bioinformatic analysis to determine its effect on global gene expression patterns and signal transduction pathways. Our results indicated that rAAV-Vastatin significantly reduced the expressions of Pck1, JAG2, and c-Fos, thus inhibiting the cellular metabolism, Notch and AP-1 signaling pathways, respectively. Hence, we demonstrated for the first time that Vastatin is a novel, safe, and effective antiangiogenic therapeutic and a potential biomarker for HCC.-
dc.languageeng-
dc.relation.ispartofMolecular Therapy-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleVastatin, an Endogenous Antiangiogenesis Polypeptide That Is Lost in Hepatocellular Carcinoma, Effectively Inhibits Tumor Metastasis-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/mt.2016.56-
dc.identifier.pmid26961408-
dc.identifier.pmcidPMC5023388-
dc.identifier.scopuseid_2-s2.0-84985916913-
dc.identifier.volume24-
dc.identifier.issue8-
dc.identifier.spage1358-
dc.identifier.epage1368-
dc.identifier.eissn1525-0024-
dc.identifier.isiWOS:000383280900007-

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