Expression of thrombospondin-1 and Ski are prognostic factors in advanced gastric cancer
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.
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.
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.
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.
KeywordsThrombospondin-1 Gastric cancer Ski TGF-β Prognosis VEGF
Grant support was provided by the Research Support Foundation of The University of Tokushima and TAIHO Pharmaceutical Co., Ltd.
Conflict of interest
There is no conflict of interest to declare.
- 1.World Health Organization. http://www.who.int/mediacentre/factsheets/fs297/en/