Stanniocalcin-1 Reduces Tumor Size in Human Hepatocellular Carcinoma

Growing 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 e...

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Main Authors:	Yeung, Bonnie H. Y., Shek, Felix H., Lee, Nikki P., Wong, Chris K. C.
Format:	Online
Language:	English
Published:	Public Library of Science 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607425/

id	pubmed-4607425
recordtype	oai_dc
spelling	pubmed-46074252015-10-29 Stanniocalcin-1 Reduces Tumor Size in Human Hepatocellular Carcinoma Yeung, Bonnie H. Y. Shek, Felix H. Lee, Nikki P. Wong, Chris K. C. Research Article Growing 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 overexpression 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. Public Library of Science 2015-10-15 /pmc/articles/PMC4607425/ /pubmed/26469082 http://dx.doi.org/10.1371/journal.pone.0139977 Text en © 2015 Yeung et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Yeung, Bonnie H. Y. Shek, Felix H. Lee, Nikki P. Wong, Chris K. C.
spellingShingle	Yeung, Bonnie H. Y. Shek, Felix H. Lee, Nikki P. Wong, Chris K. C. Stanniocalcin-1 Reduces Tumor Size in Human Hepatocellular Carcinoma
author_facet	Yeung, Bonnie H. Y. Shek, Felix H. Lee, Nikki P. Wong, Chris K. C.
author_sort	Yeung, Bonnie H. Y.
title	Stanniocalcin-1 Reduces Tumor Size in Human Hepatocellular Carcinoma
title_short	Stanniocalcin-1 Reduces Tumor Size in Human Hepatocellular Carcinoma
title_full	Stanniocalcin-1 Reduces Tumor Size in Human Hepatocellular Carcinoma
title_fullStr	Stanniocalcin-1 Reduces Tumor Size in Human Hepatocellular Carcinoma
title_full_unstemmed	Stanniocalcin-1 Reduces Tumor Size in Human Hepatocellular Carcinoma
title_sort	stanniocalcin-1 reduces tumor size in human hepatocellular carcinoma
description	Growing 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 overexpression 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.
publisher	Public Library of Science
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607425/
_version_	1613488771739680768

Stanniocalcin-1 Reduces Tumor Size in Human Hepatocellular Carcinoma

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