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Article: Stanniocalcin-1 Reduces Tumor Size in Human Hepatocellular Carcinoma

TitleStanniocalcin-1 Reduces Tumor Size in Human Hepatocellular Carcinoma
Authors
Issue Date2015
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2015, v. 10 n. 10, p. e0139977 How to Cite?
AbstractGrowing evidence has revealed high expression levels of stanniocalcin-1 (STC1) in different types of human cancers. Numerous experimental studies using cancer cell lines demonstrated the involvement of STC1 in inflammatory and apoptotic processes; however the role of STC1 in carcinogenesis remains elusive. Hepatocellular carcinoma (HCC) an exemplified model of inflammation-related cancer, represents a paradigm of studying the association between STC1 and tumor development. Therefore, we conducted a statistical analysis on the expression levels of STC1 using clinicopathological data from 216 HCC patients. We found that STC1 was upregulated in the tumor tissues and its expression levels was positively correlated with the levels of interleukin (IL)-6 and IL-8. Intriguingly tumors with greater expression levels of STC1 (tumor/normal >= 2) were significantly smaller than the lower level (tumor/normal<2) samples (p = 0.008). A pharmacological approach was implemented to reveal the functional correlation between STC1 and the ILs in the HCC cell-lines. IL-6 and IL-8 treatment of Hep3B cells induced STC1 expression. Lentiviral-based STC1 over-expression in Hep3B and MHCC-97L cells however showed inhibitory action on the pro-migratory effects of IL-6 and IL-8 and reduced size of tumor spheroids. The inhibitory effect of STC1 on tumor growth was confirmed in vivo using the stable STC1-overexpressing 97L cells on a mouse xenograft model. Genetic analysis of the xenografts derived from the STC1-overexpressing 97L cells, showed upregulation of the pro-apoptotic genes interleukin-12 and NOD-like receptor family, pyrin domain-containing 3. Collectively, the anti-inflammatory and pro-apoptotic functions of STC1 were suggested to relate its inhibitory effect on the growth of HCC cells. This study supports the notion that STC1 may be a potential therapeutic target for inflammatory tumors in HCC patients.
Persistent Identifierhttp://hdl.handle.net/10722/227871
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYeung, BHY-
dc.contributor.authorShek, FH-
dc.contributor.authorLee, PY-
dc.contributor.authorWong, CKC-
dc.date.accessioned2016-07-21T06:11:01Z-
dc.date.available2016-07-21T06:11:01Z-
dc.date.issued2015-
dc.identifier.citationPlos One, 2015, v. 10 n. 10, p. e0139977-
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/10722/227871-
dc.description.abstractGrowing evidence has revealed high expression levels of stanniocalcin-1 (STC1) in different types of human cancers. Numerous experimental studies using cancer cell lines demonstrated the involvement of STC1 in inflammatory and apoptotic processes; however the role of STC1 in carcinogenesis remains elusive. Hepatocellular carcinoma (HCC) an exemplified model of inflammation-related cancer, represents a paradigm of studying the association between STC1 and tumor development. Therefore, we conducted a statistical analysis on the expression levels of STC1 using clinicopathological data from 216 HCC patients. We found that STC1 was upregulated in the tumor tissues and its expression levels was positively correlated with the levels of interleukin (IL)-6 and IL-8. Intriguingly tumors with greater expression levels of STC1 (tumor/normal >= 2) were significantly smaller than the lower level (tumor/normal<2) samples (p = 0.008). A pharmacological approach was implemented to reveal the functional correlation between STC1 and the ILs in the HCC cell-lines. IL-6 and IL-8 treatment of Hep3B cells induced STC1 expression. Lentiviral-based STC1 over-expression in Hep3B and MHCC-97L cells however showed inhibitory action on the pro-migratory effects of IL-6 and IL-8 and reduced size of tumor spheroids. The inhibitory effect of STC1 on tumor growth was confirmed in vivo using the stable STC1-overexpressing 97L cells on a mouse xenograft model. Genetic analysis of the xenografts derived from the STC1-overexpressing 97L cells, showed upregulation of the pro-apoptotic genes interleukin-12 and NOD-like receptor family, pyrin domain-containing 3. Collectively, the anti-inflammatory and pro-apoptotic functions of STC1 were suggested to relate its inhibitory effect on the growth of HCC cells. This study supports the notion that STC1 may be a potential therapeutic target for inflammatory tumors in HCC patients.-
dc.languageeng-
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action-
dc.relation.ispartofPlos One-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleStanniocalcin-1 Reduces Tumor Size in Human Hepatocellular Carcinoma-
dc.typeArticle-
dc.identifier.emailLee, PY: nikkilee@hkucc.hku.hk, puiyue@wokans.com-
dc.identifier.authorityLee, PY=rp00263-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0139977-
dc.identifier.pmid26469082-
dc.identifier.hkuros263551-
dc.identifier.volume10-
dc.identifier.issue10-
dc.identifier.spagee0139977-
dc.identifier.epagee0139977-
dc.identifier.isiWOS:000363184600023-
dc.publisher.placeUnited States-

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