Preferential up-regulation of heparanase and cyclooxygenase-2 in carcinogenesis of Barrett's oesophagus and intestinal-type gastric carcinoma.
OBJECTIVE
Metaplastic changes secondary to chronic inflammation at the gastro-oesophageal junction and at the pyloric antrum are recognized as the premalignant conditions of Barrett's oesophageal adenocarcinoma and intestinal-type gastric carcinoma (GC), respectively. Heparanase (HPSE) and cyclooxygenase (COX)-2 have been proved to play critical roles in inflammation as well as in cancer. The aim was to examine the meaning of their expression in inflammation-related carcinogenesis.


RESULTS
First, expression of HPSE and COX-2 in 78 clinical tissues of Barrett's oesophagus was examined by immunohistochemistry and in situ hybridization. Their expression was increased during the metaplasia-dysplasia sequence with increased neovascularization. Successively, their expression in Barrett's dysplasia was compared with that of GC (22 cases of diffuse-type and 10 of intestinal-type). Interestingly, the expression pattern in Barrett's dysplasia was similar to that in intestinal-type GC, which mainly arises from chronic inflammation. Furthermore, cultured cell lines isolated from differentiated GC tissues, which are often found to be of intestinal-type, revealed up-regulated mRNA expression of HPSE and COX-2.


CONCLUSIONS
HPSE and COX-2 are preferentially up-regulated in Barrett's oesophagus and intestinal-type GC. These molecules may play an important role during the development of inflammation-related adenocarcinoma of the upper gastrointestinal tract.
Sonoda
Ryotaro
R
Department of Gastroenterological Surgery, Transplant, and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Naomoto
Yoshio
Y
Shirakawa
Yasuhiro
Y
Fujiwara
Yasuhiro
Y
Yamatsuji
Tomoki
T
Noma
Kazuhiro
K
Tanabe
Shunsuke
S
Takaoka
Munenori
M
Gunduz
Mehmet
M
Tsujigiwa
Hidetsugu
H
Nagatsuka
Hitoshi
H
Ohara
Nobuya
N
Yoshino
Tadashi
T
Takubo
Kaiyo
K
Vieth
Michael
M
Tanaka
Noriaki
N
D000230:Adenocarcinoma / Q000098:blood supply / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D001471:Barrett Esophagus / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D001483:Base Sequence; D002278:Carcinoma in Situ / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D004938:Esophageal Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D055806:Microvessels / Q000473:pathology; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology; D015854:Up-Regulation; D000099175:Heparanase
D051546:Cyclooxygenase 2; D017931:DNA Primers; D005966:Glucuronidase; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000099175:Heparanase