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Journal of Environmental Pathology, Toxicology and Oncology

ISSN for PRINT: 0731-8898

Institutional price:	$672.00
Issues per year:	4

Best Paper Award Selection - Editorial Board Site

2002, Volume21

124 pages

Issue price - $160.00

Increased Expression of COX-2 in the Development of Human Lung Cancers

Takashi Takahashi
Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan

Ken-ichi Kozaki
Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan

Yasushi Yatabe
Department of Pathology and Clinical Laboratories, Aichi Cancer Center Hospital, Nagoya, Japan

Hiroyuki Achiwa
Department of Internal Medicine, Aichi Cancer Center Hospital, Nagoya, Japan

Toyoaki Hida
Department of Internal Medicine, Aichi Cancer Center Hospital, Nagoya, Japan

ABSTRACT

It is well accepted that an increase in the expression of cyclooxygenase-2 (COX-2), a key inducible enzyme involved in the production of prostaglandins and other eicosanoids, may play a significant role in carcinogenesis in addition to its well-known role in inflammatory reactions. Whereas previous studies were largely confined to colorectal tumorigenesis, we have shown that a significantly increased expression of COX-2 may also play a role in the development of lung cancer. COX-2 expression was found to be frequently elevated in lung cancer, especially in adenocarcinoma, and the proportion of lung cancer cells with marked COX-2 expression was much higher in lymph node metastases than in the corresponding primary tumors. It was also shown that early stage adenocarcinoma patients with increased COX-2 expression who were surgically treated had a shorter survival. Our studies, which used high- and low-metastatic human lung cancer cell sublines established in our laboratory, revealed an association between metastatic capabilities and COX-2 expression levels: COX-2-specific inhibitors could inhibit in vitro the invasion of the highly metastatic NCI-H460-LNM35 clone through Matrigel-containing basement membrane components as well as the spontaneous in vivo metastasis in SCID mice. Taken together, these findings suggest that an increase in COX-2 expression may be associated with the development of lung cancer and possibly with the acquisition of an invasive and metastatic phenotype.