Journal
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY
Volume 16, Issue 2, Pages 145-152Publisher
SPRINGER JAPAN KK
DOI: 10.1007/s10147-010-0147-5
Keywords
Thrombospondin-1; Gastric cancer; Ski; TGF-beta; Prognosis; VEGF
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Funding
- Research Support Foundation of The University of Tokushima
- TAIHO Pharmaceutical Co., Ltd.
- Grants-in-Aid for Scientific Research [22659233] Funding Source: KAKEN
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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-beta (TGF-beta). Recent studies have shown that Ski protein suppresses TGF-beta 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-beta 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-beta 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-beta-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-beta for survival in advanced gastric cancer.
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