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Molecular Cancer

, 13:225

First Online: 28 September 2014Received: 11 December 2013Accepted: 22 September 2014DOI: 10.1186-1476-4598-13-225

Cite this article as: Sun, R., Wu, J., Chen, Y. et al. Mol Cancer 2014 13: 225. doi:10.1186-1476-4598-13-225

Abstract

BackgroundThrombospondins THBSs are a family of multidomain and secreted matricellular Ca-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.

MethodsThe 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.

Results85.71% 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.

ConclusionOur 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.

KeywordsTHBS2 Gastric cancer Angiogenesis Prognostic biomarker Electronic supplementary materialThe online version of this article doi:10.1186-1476-4598-13-225 contains supplementary material, which is available to authorized users.

Ruochuan Sun, Jifeng Wu, Yuanyuan Chen contributed equally to this work.

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Autor: Ruochuan Sun - Jifeng Wu - Yuanyuan Chen - Mingdian Lu - Shangxin Zhang - Daru Lu - Yongxiang Li

Fuente: https://link.springer.com/



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