Abstract
BackgroundThrombospondins (THBSs) are a family of multidomain and secreted matricellular Ca2+-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.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-4598-13-225) contains supplementary material, which is available to authorized users.
Highlights
Gastric cancer is a highly aggressive and lethal malignancy
We found THBS2 proteins were mainly expressed in the cytoplasms of gastric cells (Figure 2A), and in accordance with the results of western blot, the levels of THBS2 were significantly inhibited in gastric cancer tissues compared with the normal controls (Figure 2B, P < 0.05)
Our results demonstrates that THBS2 is down-regulated in gastric cancer in both mRNA and protein levels
Summary
A total of 952,000 new stomach cancer cases and 723,000 deaths were estimated to have occurred in 2012, accounting for 6.8% of the total cases and 8.8% of total deaths Both new cases and deaths of gastric cancer in China, ranked 1st globally, accounting for over 40%. Thrombospondins (THBSs) are a family of multidomain and matricellular Ca2+-binding glycoproteins secreted by stromal fibroblasts, endothelial cells and immune cells [2]. They have at least five members encoded by independent genes. Thrombospondins (THBSs) are a family of multidomain and secreted matricellular Ca2+-binding glycoproteins which has at least five members encoded by independent genes. The functions and clinical significance of THBS2 still remains unclear in gastric cancer
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