The close relationship between heparanase and cyclooxygenase-2 expressions in signet-ring cell carcinoma of the stomach.
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.
Ohtawa
Yasuyuki
Y
Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Naomoto
Yoshio
Y
Shirakawa
Yasuhiro
Y
Takaoka
Munenori
M
Murata
Toshihiro
T
Sonoda
Ryotaro
R
Sakurama
Kazufumi
K
Yamatsuji
Tomoki
T
Gunduz
Mehmet
M
Tsujigiwa
Hidetsugu
H
Nagatsuka
Hitoshi
H
Terada
Norihiko
N
Itano
Satoshi
S
Horiki
Sadayuki
S
Yanagihara
Kazuyoshi
K
Nakajima
Motowo
M
Tanaka
Noriaki
N
D000328:Adult; D000367:Age Factors; D000368:Aged; D018279:Carcinoma, Signet Ring Cell / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D005260:Female; D005966:Glucuronidase / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology; D000099175:Heparanase
D051546:Cyclooxygenase 2; D005966:Glucuronidase; D012333:RNA, Messenger; D000099175:Heparanase