Stanniocalcin-1 Reduces Tumor Size in Human Hepatocellular Carcinoma.

Bonnie H Y Yeung,Nikki P Lee,Felix H Shek,Chris K C Wong

doi:10.1371/journal.pone.0139977

Bonnie H Y Yeung, Nikki P Lee + Show 2 more

Open Access

https://doi.org/10.1371/journal.pone.0139977

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Journal: PloS one	Publication Date: Oct 15, 2015
Citations: 23	License type: CC BY 4.0

Affiliation: University of Hong Kong, Hong Kong Baptist University

Abstract

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.

Highlights

Stanniocalcin-1 (STC1) is a hypocalcemic hormone, synthesized and secreted by a unique endocrine gland, corpuscles of Stannius (CS) in bony fish
Since Hepatocellular carcinoma (HCC) is an exemplified model of inflammation-related cancer, it represents a paradigm of studying the association between STC1 and tumor development
STC1 was found to be highly expressed in tumor tissues versus the adjacent normal counterpart, collected from the HCC cases

Summary

Introduction

Stanniocalcin-1 (STC1) is a hypocalcemic hormone, synthesized and secreted by a unique endocrine gland, corpuscles of Stannius (CS) in bony fish. There is no CS gland or any comparable structure found in mammals, the STC1 gene was believed to have been lost in evolution. The mammalian forms of STC1, were cloned in gene-screening experiments using. Studies intended to mirror the fish data and to validate the endocrine effects of STC1 on Ca2+ homeostasis in mammals. Many studies illustrated the mammalian STC1 exerts its functions via paracrine/autocrine pathways [5], which is different from the action reported in fish models. Considerable studies reported the involvement of the mammalian STC1 in processes of inflammation and carcinogenesis [7]

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