Expression of thrombospondin-1 and Ski are prognostic factors in advanced gastric cancer.
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.
Department of Surgery, Institute of Health Bioscience, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
Toshihiro
T
Nakao
Nobuhiro
N
Kurita
Masato
M
Komatsu
Kozo
K
Yoshikawa
Takashi
T
Iwata
Toru
T
Utsunomiya
Mitsuo
M
Shimada
D000368:Aged; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D055806:Microvessels / Q000378:metabolism; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013534:Survival; D019700:Thrombospondin 1 / Q000096:biosynthesis* / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D019700:Thrombospondin 1; D016212:Transforming Growth Factor beta; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C060614:SKI protein, human