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International Journal of Clinical Oncology

Erschienen in:

01.04.2011 | Original Article

Expression of thrombospondin-1 and Ski are prognostic factors in advanced gastric cancer

verfasst von: Toshihiro Nakao, Nobuhiro Kurita, Masato Komatsu, Kozo Yoshikawa, Takashi Iwata, Toru Utsunomiya, Mitsuo Shimada

Erschienen in: International Journal of Clinical Oncology | Ausgabe 2/2011

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Abstract

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.

World Health Organization. http://www.who.int/mediacentre/factsheets/fs297/en/

Parkin DM, Bray F, Ferlay J et al (2005) Global cancer statistics, 2002. CA Cancer J Clin 55(2):74–108PubMedCrossRef

Ganguly P (1971) Isolation and properties of a thrombin-sensitive protein from human blood platelets. J Biol Chem 246(13):4286–4290PubMed

Maeda K, Nishiguchi Y, Kang SM et al (2001) Expression of thrombospondin-1 inversely correlated with tumor vascularity and hematogenous metastasis in colon cancer. Oncol Rep 8(4):763–766PubMed

Yamaguchi M, Sugio K, Ondo K et al (2002) Reduced expression of thrombospondin-1 correlates with a poor prognosis in patients with non-small cell lung cancer. Lung Cancer 36(2):143–150PubMedCrossRef

Grossfeld GD, Ginsberg DA, Stein JP et al (1997) Thrombospondin-1 expression in bladder cancer: association with p53 alterations, tumor angiogenesis, and tumor progression. J Natl Cancer Inst 89(3):219–227PubMedCrossRef

Morelli D, Lazzerini D, Cazzaniga S et al (1998) Evaluation of the balance between angiogenic and antiangiogenic circulating factors in patients with breast and gastrointestinal cancers. Clin Cancer Res 4(5):1221–1225PubMed

Kasper HU, Ebert M, Malfertheiner P et al (2001) Expression of thrombospondin-1 in pancreatic carcinoma: correlation with microvessel density. Virchows Arch 438:116–120PubMedCrossRef

Yamashita Y, Kurohiji T, Tuszynski GP et al (1998) Plasma thrombospondin levels in patients with colorectal carcinoma. Cancer 82:632–638PubMedCrossRef

10.

Heldin CH, Miyazono K, ten Dijke P (1997) TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature 390:465–471PubMedCrossRef

11.

Maeda K, Nishiguchi Y, Yashiro M et al (2000) Expression of vascular endothelial growth factor and thrombospondin-1 in colorectal carcinoma. Int J Mol Med 5:373–378PubMed

12.

Poon RT, Chung KK, Cheung ST et al (2004) Clinical significance of thrombospondin 1 expression in hepatocellular carcinoma. Clin Cancer Res 10:4150–4157PubMedCrossRef

13.

Pratt DA, Miller WR, Dawes J (1989) Thrombospondin in malignant and non-malignant breast tissue. Eur J Cancer Clin Oncol 25:343–350PubMedCrossRef

14.

Luo Ski K, Sno N (2004) Negative regulators of TGF-beta signaling. Curr Opin Genet Dev 14:65–70CrossRef

15.

Zhang J, Ito R, Oue N et al (2003) Expression of thrombospondin-1 is correlated with microvessel density in gastric carcinoma. Virchows Arch 442:563–568PubMed

16.

Takahata M, Inoue Y, Tsuda H et al (2009) SKI and MEL1 cooperate to inhibit transforming growth factor-beta signal in gastric cancer cells. J Biol Chem 284:3334–3344PubMedCrossRef

17.

Saito H, Tsujitani S, Ikeguchi M et al (1998) Relationship between the expression of vascular endothelial growth factor and the density of dendritic cells in gastric adenocarcinoma tissue. Br J Cancer 78:1573–1577PubMedCrossRef

18.

Saito H, Tsujitani S, Oka S et al (1999) The expression of transforming growth factor-beta1 is significantly correlated with the expression of vascular endothelial growth factor and poor prognosis of patients with advanced gastric carcinoma. Cancer 86:1455–1462PubMedCrossRef

19.

Vermeulen PB, Gasparini G, Fox SB et al (1996) Quantification of angiogenesis in solid human tumours: an international consensus on the methodology and criteria of evaluation. Eur J Cancer 32A:2474–2484PubMedCrossRef

20.

Fondevila C, Metges JP, Fuster J et al (2004) p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer. Br J Cancer 90:206–215PubMedCrossRef

21.

Greenaway J, Lawler J, Moorehead R et al (2007) Thrombospondin-1 inhibits VEGF levels in the ovary directly by binding and internalization via the low density lipoprotein receptor-related protein-1 (LRP-1). J Cell Physiol 210:807–818PubMedCrossRef

22.

Poon RT, Chung KK, Cheung ST et al (2004) Clinical significance of thrombospondin 1 expression in hepatocellular carcinoma. Clin Cancer Res 10:4150–4157PubMedCrossRef

23.

Hironaka S, Hasebe T, Kamijo T et al (2002) Biopsy specimen microvessel density is a useful prognostic marker in patients with T(2–4)M(0) esophageal cancer treated with chemoradiotherapy. Clin Cancer Res 8:124–130PubMed

24.

Kiyono K, Suzuki HI, Morishita Y et al (2009) c-Ski overexpression promotes tumor growth and angiogenesis through inhibition of transforming growth factor-beta signaling in diffuse-type gastric carcinoma. Cancer Sci 100:1809–1816PubMedCrossRef

Titel: Expression of thrombospondin-1 and Ski are prognostic factors in advanced gastric cancer
verfasst von: Toshihiro Nakao
Nobuhiro Kurita
Masato Komatsu
Kozo Yoshikawa
Takashi Iwata
Toru Utsunomiya
Mitsuo Shimada
Publikationsdatum: 01.04.2011
Verlag: Springer Japan
Erschienen in: International Journal of Clinical Oncology / Ausgabe 2/2011
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-010-0147-5

Springer Medizin

Expression of thrombospondin-1 and Ski are prognostic factors in advanced gastric cancer