Immunohistochemical expression of COX-2, mPGES and EP2 receptor in normal and reactive canine bone and in canine osteosarcoma.
Accumulating evidence suggests that cyclooxygenase (COX)-2 is involved in the pathogenesis of human and canine osteosarcoma. The aim of this study was to investigate the expression of COX-2 in normal, reactive and neoplastic canine bone and the events downstream to COX-2 that lead to prostaglandin E(2) (PGE(2)) production. COX-2, microsomal PGE(2) synthase-1 (mPGES-1) and the PGE(2) receptor (EP2) were assessed by immunohistochemistry in 12 samples of normal bone, 14 cases of fracture callus and 27 appendicular osteosarcomas. No immunoreactivity to COX-2, mPGES-1 or EP2 receptor was observed in normal bone. Fifty percent of reactive bone samples expressed COX-2 and 57% expressed mPGES-1 and EP2 receptor, although with weak labelling intensity. Ninety-three percent of osteosarcomas expressed COX-2, while mPGES-1 was expressed by 85% and EP2 receptor by 89% of the tumours. The data confirm that COX-2 is expressed at high level in osteosarcoma and support the use of COX-2 inhibitors to improve the response to chemotherapy. The possibility of blocking the EP2 or the selective inhibition of mPGES-1, rather than COX-2 activity, might decrease the incidence of adverse effects that occur due to the inhibition of prostanoids other than PGE(2).
Dipartimento di Patologia Animale, Profilassi ed Igiene degli Alimenti, Facoltà di Medicina Veterinaria, University of Pisa, Pisa I-56124, Italy.
F
F
Millanta
P
P
Asproni
S
S
Cancedda
M
M
Vignoli
B
B
Bacci
A
A
Poli
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D001842:Bone and Bones / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004283:Dog Diseases / Q000473:pathology*; D004285:Dogs; D005260:Female; D008297:Male; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000378:metabolism*
D014408:Biomarkers, Tumor; D058307:Receptors, Prostaglandin E, EP2 Subtype; D051546:Cyclooxygenase 2; D015232:Dinoprostone