Background: It has been suggested that thrombospondin-1 (TSP-1) plays a role in angiogenesis in many cancers. In addition, TSP-1 has been shown to suppress tumor growth by activating transforming growth factor-β (TGF-β). Recent studies have shown that Ski protein suppresses TGF-β signaling. The aim of this study was to investigate the role of TSP-1 and Ski expression in advanced gastric cancer.
Methods: Sixty-five recurrent patients who underwent resection of advanced gastric cancer (n = 62) or who had unresectable tumors (n = 3) between March 2003 and October 2007 participated in this study. All patients were treated with chemotherapy after collection of the tumor tissue. Twenty-three of them were also treated with chemotherapy before collection of the tumor specimen. The TSP-1, Ski, vascular endothelial growth factor (VEGF) and TGF-β protein expression were examined by immunohistochemical staining, and microvessels in the tumor were counted.
Results: There were 17 (26.2%) gastric cancers with positive staining for TSP-1. There was no relationship between TSP-1 expression and clinicopathological factors. TSP-1 expression had positive association with VEGF expression, microvessel density (MVD) and TGF-β expression. However, there was no relationship between TSP-1 and Ski expression. TSP-1 correlated with good survival in advanced gastric cancer, and Ski correlated with poor survival in the patients with TGF-β-positive advanced gastric cancer.
Conclusions: This study shows that TSP-1 enhances angiogenesis due to its positive correlation with VEGF and MVD, and is a good prognostic factor for survival in advanced gastric cancer. This study also shows that Ski inhibits the prolonged effects of TGF-β for survival in advanced gastric cancer.