Expression of cyclo-oxygenase-2 in naturally occurring squamous cell carcinomas in dogs

Squamous cell carcinoma is one of the most common cancers in humans and is also a frequently diagnosed neoplasm in dogs. Induction of cyclo-oxygenase- 2 (COX-2), a key rate-limiting enzyme in prostaglandin biosynthesis, has be en implicated in the oncogenesis of Various cancers in humans, including sq uamous cell carcinomas. However, expression of COX-2 has not been reported in spontaneous squamous cell carcinomas of nonhuman species. Canine squamou s cell carcinomas share several similarities with the human disease. Theref ore, the objective of this study was to determine whether COX isoenzymes we re expressed in naturally occurring cases of squamous cell carcinomas in do gs. Canine normal skin (n=4) and squamous cell carcinomas (n=40) were studi ed by immunohistochemistry and immunoblotting analysis using polyclonal ant ibodies selective for COX-1 or COX-2. COX-2 was strongly expressed by neopl astic keratinocytes in all cases of squamous cell carcinomas, whereas no CO X-2 was detected in normal skin and in the non-neoplastic skin and oral muc osa included in the tumor tissue samples (p <0.01). Immunoblotting analysis confirmed the restricted expression of COX-2 (72,000-74,000 molecular weig ht doublet) in squamous cell carcinomas only. In contrast, faint COX-1 stai ning was found in normal skin and in squamous cell carcinomas. This study d emonstrates for the first time that COX-2 is induced in canine squamous cel l carcinomas, and provides a new model to investigate the role and regulati on of COX-2 gene expression in naturally occurring squamous cell carcinomas .