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Heparanase expression correlates with malignant potential in human colon cancer

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Abstract

Purpose

Heparanase cleaves carbohydrate chains of heparan sulphate proteoglycans and is an important component of the extracellular matrix. This study was designed to determine the relation between heparanase expression and prognosis of patients with colon cancer.

Methods

The study included 54 patients (35 males and 19 females) who underwent colorectal resection for colorectal cancer between January 1992 and December 1994. Expression of heparanase protein and mRNA were determined and correlated with various clinicopathological parameters. In vitro studies were also performed to examine tumor invasion and to test the effects of heparanase inhibition, and in vivo studies were performed to examine tumor metastasis and prognosis.

Results

Heparanase expression was detected in the invasion front of the tumor in 37 of 54 (69%) colon cancer samples, whereas 17 of 54 (31%) tumors were negative. Expression of heparanase was significantly more frequent in tumors of higher TNM stage (P=0.0481), higher Dukes stage (P=0.0411), higher vascular infiltration (P=0.0146), and higher lymph vessel infiltration (P=0.0010). Heparanase expression in colon cancers correlated significantly with poor survival (P=0.0361). Heparanase-transfected colon cancer cells exhibited significant invasion compared with control-transfected colon cancer cells (P=0.001), and the peritoneal dissemination model also showed the malignant potential of heparanase-transfected cells, as assayed by number of nodules (P=0.017) and survival (P=0.0062). Inhibition of heparanase significantly reduced the invasive capacity of cancer cells (P=0.003).

Conclusions

Heparanase is a marker for poor prognosis of patients with colon cancer and could be a suitable target for antitumor therapy in colon cancer.

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Acknowledgements

We thank Tae Yamanishi, Yoshiko Shirakiya, and Masahide Sakurai for their excellent technical assistance and our colleagues for valuable scientific advice

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Authors and Affiliations

  1. Department of Gastroenterological Surgery Transplant and Surgical Oncology, Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan

    T. Nobuhisa, Y. Naomoto, T. Ohkawa, M. Takaoka, R. Ono, T. Murata, Y. Shirakawa, T. Yamatsuji, M. Haisa, J. Matsuoka & N. Tanaka

  2. Departmentof Oral Pathology and Medicine, Graduate School of Medicine and Dentistry, Okayama, Japan

    M. Gunduz, H. Tsujigiwa & H. Nagatsuka

  3. Tsukuba Research Institute, Novartis Pharma KK, Tsukuba, Japan

    M. Nakajima

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  1. T. Nobuhisa
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  2. Y. Naomoto
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  3. T. Ohkawa
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  4. M. Takaoka
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  5. R. Ono
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  12. H. Tsujigiwa
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  14. M. Nakajima
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  15. N. Tanaka
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Correspondence to Y. Naomoto.

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Nobuhisa, T., Naomoto, Y.., Ohkawa, T. et al. Heparanase expression correlates with malignant potential in human colon cancer. J Cancer Res Clin Oncol 131, 229–237 (2005). https://doi.org/10.1007/s00432-004-0644-x

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  • DOI: https://doi.org/10.1007/s00432-004-0644-x

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