Heparanase expression correlates with malignant potential in human colon cancer

T. Nobuhisa, Y. Naomoto, T. Ohkawa, M. Takaoka, R. Ono, T. Murata, M. Gunduz, Yasuhiro Shirakawa, T. Yamatsuji, M. Haisa, Junji Matsuoka, H. Tsujigiwa, Hitoshi Nagatsuka, M. Nakajima, N. Tanaka

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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 = 0001), 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.

Original languageEnglish
Pages (from-to)229-237
Number of pages9
JournalJournal of Cancer Research and Clinical Oncology
Volume131
Issue number4
DOIs
Publication statusPublished - Apr 2005

Fingerprint

Colonic Neoplasms
Neoplasms
heparanase
Heparan Sulfate Proteoglycans
Survival
Lymph
Extracellular Matrix
Blood Vessels
Colorectal Neoplasms
Carbohydrates
Neoplasm Metastasis
Messenger RNA

Keywords

  • Colon cancer
  • Heparanase
  • Malignancy
  • Prognosis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Nobuhisa, T., Naomoto, Y., Ohkawa, T., Takaoka, M., Ono, R., Murata, T., ... Tanaka, N. (2005). Heparanase expression correlates with malignant potential in human colon cancer. Journal of Cancer Research and Clinical Oncology, 131(4), 229-237. https://doi.org/10.1007/s00432-004-0644-x

Heparanase expression correlates with malignant potential in human colon cancer. / Nobuhisa, T.; Naomoto, Y.; Ohkawa, T.; Takaoka, M.; Ono, R.; Murata, T.; Gunduz, M.; Shirakawa, Yasuhiro; Yamatsuji, T.; Haisa, M.; Matsuoka, Junji; Tsujigiwa, H.; Nagatsuka, Hitoshi; Nakajima, M.; Tanaka, N.

In: Journal of Cancer Research and Clinical Oncology, Vol. 131, No. 4, 04.2005, p. 229-237.

Research output: Contribution to journalArticle

Nobuhisa, T, Naomoto, Y, Ohkawa, T, Takaoka, M, Ono, R, Murata, T, Gunduz, M, Shirakawa, Y, Yamatsuji, T, Haisa, M, Matsuoka, J, Tsujigiwa, H, Nagatsuka, H, Nakajima, M & Tanaka, N 2005, 'Heparanase expression correlates with malignant potential in human colon cancer', Journal of Cancer Research and Clinical Oncology, vol. 131, no. 4, pp. 229-237. https://doi.org/10.1007/s00432-004-0644-x
Nobuhisa, T. ; Naomoto, Y. ; Ohkawa, T. ; Takaoka, M. ; Ono, R. ; Murata, T. ; Gunduz, M. ; Shirakawa, Yasuhiro ; Yamatsuji, T. ; Haisa, M. ; Matsuoka, Junji ; Tsujigiwa, H. ; Nagatsuka, Hitoshi ; Nakajima, M. ; Tanaka, N. / Heparanase expression correlates with malignant potential in human colon cancer. In: Journal of Cancer Research and Clinical Oncology. 2005 ; Vol. 131, No. 4. pp. 229-237.
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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 = 0001), 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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T1 - Heparanase expression correlates with malignant potential in human colon cancer

AU - Nobuhisa, T.

AU - Naomoto, Y.

AU - Ohkawa, T.

AU - Takaoka, M.

AU - Ono, R.

AU - Murata, T.

AU - Gunduz, M.

AU - Shirakawa, Yasuhiro

AU - Yamatsuji, T.

AU - Haisa, M.

AU - Matsuoka, Junji

AU - Tsujigiwa, H.

AU - Nagatsuka, Hitoshi

AU - Nakajima, M.

AU - Tanaka, N.

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N2 - 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 = 0001), 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.

AB - 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 = 0001), 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.

KW - Colon cancer

KW - Heparanase

KW - Malignancy

KW - Prognosis

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