The close relationship between heparanase and cyclooxygenase-2 expressions in signet-ring cell carcinoma of the stomach

Yasuyuki Ohtawa, Yoshio Naomoto, Yasuhiro Shirakawa, Munenori Takaoka, Toshihiro Murata, Ryotaro Sonoda, Kazufumi Sakurama, Tomoki Yamatsuji, Mehmet Gunduz, Hidetsugu Tsujigiwa, Hitoshi Nagatsuka, Norihiko Terada, Satoshi Itano, Sadayuki Horiki, Kazuyoshi Yanagihara, Motowo Nakajima, Noriaki Tanaka

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Signet-ring cell carcinoma (SRC) of the stomach exhibits diffuse growth and invasion without forming ducts. Destruction of the surrounding basal membrane and angiogenesis appear to be required for SRC to exhibit marked invasion and growth. We recently reported that heparanase (HPA) and cyclooxygenase-2 (COX-2) were strongly correlated with microvessel density, and that COX-2 expression is up-regulated by HPA in esophageal cancer. In this study, we examined the relationship between HPA expression and that of COX-2 in SRC of the stomach. We examined HPA and COX-2 expression in 3 cell lines derived from SRC of the stomach and in 50 SRC lesions of stomach by immunohistochemistry (IHC), in situ hybridization, and reverse transcriptase-polymerase chain reaction (RT-PCR). We also examined the relationships among HPA expression, COX-2 expression, and the clinicopathologic features of SRC, mean age, sex, invasion depth, regional lymph node metastasis, lymphatic invasion, and venous blood vessel invasion. Of the 3 cell lines, 2 exhibited both HPA and COX-2 mRNA expression on RT-PCR. Of the 3 cell lines, 1 exhibited only HPA mRNA expression on RT-PCR. Heparanase expression was confirmed in 23 (46%) of 50 tumor samples by IHC. COX-2 expression was confirmed in 25 (50%) of the 50 tumor samples by IHC. In situ hybridization revealed messenger RNA expression in the same area as in that revealed by IHC. A close correlation was noted between HPA and COX-2 expressions (P <.0001). The present study thus elucidated the biologic features of SRC of the stomach related to growth and angiogenesis.

Original languageEnglish
Pages (from-to)1145-1152
Number of pages8
JournalHuman Pathology
Volume37
Issue number9
DOIs
Publication statusPublished - Sep 2006

Fingerprint

Signet Ring Cell Carcinoma
Cyclooxygenase 2
Stomach
Reverse Transcriptase Polymerase Chain Reaction
Immunohistochemistry
Cell Line
Messenger RNA
In Situ Hybridization
Growth
Lymphatic Metastasis
heparanase
Esophageal Neoplasms
Microvessels
Blood Vessels
Neoplasms
Lymph Nodes

Keywords

  • Angiogenesis
  • COX-2
  • Gastric cancer
  • Heparanase
  • Metastasis
  • Signet-ring cell carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

The close relationship between heparanase and cyclooxygenase-2 expressions in signet-ring cell carcinoma of the stomach. / Ohtawa, Yasuyuki; Naomoto, Yoshio; Shirakawa, Yasuhiro; Takaoka, Munenori; Murata, Toshihiro; Sonoda, Ryotaro; Sakurama, Kazufumi; Yamatsuji, Tomoki; Gunduz, Mehmet; Tsujigiwa, Hidetsugu; Nagatsuka, Hitoshi; Terada, Norihiko; Itano, Satoshi; Horiki, Sadayuki; Yanagihara, Kazuyoshi; Nakajima, Motowo; Tanaka, Noriaki.

In: Human Pathology, Vol. 37, No. 9, 09.2006, p. 1145-1152.

Research output: Contribution to journalArticle

Ohtawa, Y, Naomoto, Y, Shirakawa, Y, Takaoka, M, Murata, T, Sonoda, R, Sakurama, K, Yamatsuji, T, Gunduz, M, Tsujigiwa, H, Nagatsuka, H, Terada, N, Itano, S, Horiki, S, Yanagihara, K, Nakajima, M & Tanaka, N 2006, 'The close relationship between heparanase and cyclooxygenase-2 expressions in signet-ring cell carcinoma of the stomach', Human Pathology, vol. 37, no. 9, pp. 1145-1152. https://doi.org/10.1016/j.humpath.2006.04.005
Ohtawa, Yasuyuki ; Naomoto, Yoshio ; Shirakawa, Yasuhiro ; Takaoka, Munenori ; Murata, Toshihiro ; Sonoda, Ryotaro ; Sakurama, Kazufumi ; Yamatsuji, Tomoki ; Gunduz, Mehmet ; Tsujigiwa, Hidetsugu ; Nagatsuka, Hitoshi ; Terada, Norihiko ; Itano, Satoshi ; Horiki, Sadayuki ; Yanagihara, Kazuyoshi ; Nakajima, Motowo ; Tanaka, Noriaki. / The close relationship between heparanase and cyclooxygenase-2 expressions in signet-ring cell carcinoma of the stomach. In: Human Pathology. 2006 ; Vol. 37, No. 9. pp. 1145-1152.
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abstract = "Signet-ring cell carcinoma (SRC) of the stomach exhibits diffuse growth and invasion without forming ducts. Destruction of the surrounding basal membrane and angiogenesis appear to be required for SRC to exhibit marked invasion and growth. We recently reported that heparanase (HPA) and cyclooxygenase-2 (COX-2) were strongly correlated with microvessel density, and that COX-2 expression is up-regulated by HPA in esophageal cancer. In this study, we examined the relationship between HPA expression and that of COX-2 in SRC of the stomach. We examined HPA and COX-2 expression in 3 cell lines derived from SRC of the stomach and in 50 SRC lesions of stomach by immunohistochemistry (IHC), in situ hybridization, and reverse transcriptase-polymerase chain reaction (RT-PCR). We also examined the relationships among HPA expression, COX-2 expression, and the clinicopathologic features of SRC, mean age, sex, invasion depth, regional lymph node metastasis, lymphatic invasion, and venous blood vessel invasion. Of the 3 cell lines, 2 exhibited both HPA and COX-2 mRNA expression on RT-PCR. Of the 3 cell lines, 1 exhibited only HPA mRNA expression on RT-PCR. Heparanase expression was confirmed in 23 (46{\%}) of 50 tumor samples by IHC. COX-2 expression was confirmed in 25 (50{\%}) of the 50 tumor samples by IHC. In situ hybridization revealed messenger RNA expression in the same area as in that revealed by IHC. A close correlation was noted between HPA and COX-2 expressions (P <.0001). The present study thus elucidated the biologic features of SRC of the stomach related to growth and angiogenesis.",
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AU - Takaoka, Munenori

AU - Murata, Toshihiro

AU - Sonoda, Ryotaro

AU - Sakurama, Kazufumi

AU - Yamatsuji, Tomoki

AU - Gunduz, Mehmet

AU - Tsujigiwa, Hidetsugu

AU - Nagatsuka, Hitoshi

AU - Terada, Norihiko

AU - Itano, Satoshi

AU - Horiki, Sadayuki

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KW - Metastasis

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