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Down regulation of Thrombospondin2 predicts poor prognosis in patients with gastric cancer

BACKGROUND: Thrombospondins (THBSs) are a family of multidomain and secreted matricellular Ca(2+)-binding glycoproteins which has at least five members encoded by independent genes. As a THBSs family member, Thrombospondin2 (THBS2) has been reported to regulate angiogenesis. Nevertheless, the functi...

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Autores principales: Sun, Ruochuan, Wu, Jifeng, Chen, Yuanyuan, Lu, Mingdian, Zhang, Shangxin, Lu, Daru, Li, Yongxiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189190/
https://www.ncbi.nlm.nih.gov/pubmed/25262009
http://dx.doi.org/10.1186/1476-4598-13-225
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author Sun, Ruochuan
Wu, Jifeng
Chen, Yuanyuan
Lu, Mingdian
Zhang, Shangxin
Lu, Daru
Li, Yongxiang
author_facet Sun, Ruochuan
Wu, Jifeng
Chen, Yuanyuan
Lu, Mingdian
Zhang, Shangxin
Lu, Daru
Li, Yongxiang
author_sort Sun, Ruochuan
collection PubMed
description BACKGROUND: Thrombospondins (THBSs) are a family of multidomain and secreted matricellular Ca(2+)-binding glycoproteins which has at least five members encoded by independent genes. As a THBSs family member, Thrombospondin2 (THBS2) has been reported to regulate angiogenesis. Nevertheless, the functions and clinical significance of THBS2 still remains unclear in gastric cancer. METHODS: The mRNA and protein expression levels of THBS2 were assessed in 14 paired of gastric cancer specimens and corresponding normal mucosas using quantitative real-time PCR and western blot analysis. Immunohistochemistry of THBS2 and CD34 on population-based tissue microarrays consisting of 129 gastric cancer cases were used to evaluate the prognostic significance of THBS2 and microvessel density (MVD) of each sample. Survival analyses were performed by Kaplan–Meier method and Cox’s proportional hazards model. Colony formation assay, endothelial cell tube formation assay, cell migration assay and apoptosis analysis in MKN-45 and SGC-7901 cell lines were carried out to evaluate the effects of THBS2 on gastric cancer in vitro. RESULTS: 85.71% (12 of 14) gastric cancer tissues expressed remarkably lower THBS2 in both mRNA and protein levels than the corresponding normal controls. Consistently, tissue microarray (TMA) results showed THBS2 levels were also inhibited in gastric cancer tissues compared with the normal controls. Moreover, we observed that patients with higher levels of THBS2 were significantly correlated with more favourable prognosis while decreased THBS2 expression were associated with poorer histological grades of gastric cancer. Additionally, our in vitro experiments further demonstrated that overexpression of THBS2 could impede both the proliferation rate and the tube formation of Human umbilical vein endothelial cells (HUVECs) in MKN-45 and SGC-7901 cell lines. CONCLUSION: Our study suggests THBS2 is aberrantly expressed in gastric cancer and plays a critical role in cancer progression, which can be a potential prognosis predictor of gastric cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1476-4598-13-225) contains supplementary material, which is available to authorized users.
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spelling pubmed-41891902014-10-09 Down regulation of Thrombospondin2 predicts poor prognosis in patients with gastric cancer Sun, Ruochuan Wu, Jifeng Chen, Yuanyuan Lu, Mingdian Zhang, Shangxin Lu, Daru Li, Yongxiang Mol Cancer Research BACKGROUND: Thrombospondins (THBSs) are a family of multidomain and secreted matricellular Ca(2+)-binding glycoproteins which has at least five members encoded by independent genes. As a THBSs family member, Thrombospondin2 (THBS2) has been reported to regulate angiogenesis. Nevertheless, the functions and clinical significance of THBS2 still remains unclear in gastric cancer. METHODS: The mRNA and protein expression levels of THBS2 were assessed in 14 paired of gastric cancer specimens and corresponding normal mucosas using quantitative real-time PCR and western blot analysis. Immunohistochemistry of THBS2 and CD34 on population-based tissue microarrays consisting of 129 gastric cancer cases were used to evaluate the prognostic significance of THBS2 and microvessel density (MVD) of each sample. Survival analyses were performed by Kaplan–Meier method and Cox’s proportional hazards model. Colony formation assay, endothelial cell tube formation assay, cell migration assay and apoptosis analysis in MKN-45 and SGC-7901 cell lines were carried out to evaluate the effects of THBS2 on gastric cancer in vitro. RESULTS: 85.71% (12 of 14) gastric cancer tissues expressed remarkably lower THBS2 in both mRNA and protein levels than the corresponding normal controls. Consistently, tissue microarray (TMA) results showed THBS2 levels were also inhibited in gastric cancer tissues compared with the normal controls. Moreover, we observed that patients with higher levels of THBS2 were significantly correlated with more favourable prognosis while decreased THBS2 expression were associated with poorer histological grades of gastric cancer. Additionally, our in vitro experiments further demonstrated that overexpression of THBS2 could impede both the proliferation rate and the tube formation of Human umbilical vein endothelial cells (HUVECs) in MKN-45 and SGC-7901 cell lines. CONCLUSION: Our study suggests THBS2 is aberrantly expressed in gastric cancer and plays a critical role in cancer progression, which can be a potential prognosis predictor of gastric cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1476-4598-13-225) contains supplementary material, which is available to authorized users. BioMed Central 2014-09-28 /pmc/articles/PMC4189190/ /pubmed/25262009 http://dx.doi.org/10.1186/1476-4598-13-225 Text en © Sun et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Sun, Ruochuan
Wu, Jifeng
Chen, Yuanyuan
Lu, Mingdian
Zhang, Shangxin
Lu, Daru
Li, Yongxiang
Down regulation of Thrombospondin2 predicts poor prognosis in patients with gastric cancer
title Down regulation of Thrombospondin2 predicts poor prognosis in patients with gastric cancer
title_full Down regulation of Thrombospondin2 predicts poor prognosis in patients with gastric cancer
title_fullStr Down regulation of Thrombospondin2 predicts poor prognosis in patients with gastric cancer
title_full_unstemmed Down regulation of Thrombospondin2 predicts poor prognosis in patients with gastric cancer
title_short Down regulation of Thrombospondin2 predicts poor prognosis in patients with gastric cancer
title_sort down regulation of thrombospondin2 predicts poor prognosis in patients with gastric cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189190/
https://www.ncbi.nlm.nih.gov/pubmed/25262009
http://dx.doi.org/10.1186/1476-4598-13-225
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