New bone formation in an osteoblastic tumor model is increased by endothelin-1 overexpression and decreased by endothelin A receptor blockade - 07/09/11
Abstract |
Objectives. The osteoblastic response of bone to metastatic prostate cancer is both characteristic and enigmatic. The potent vasoconstrictor endothelin-1 (ET-1), produced by prostate cancer, has been identified as a potential factor in new bone formation.
Methods. Using a novel method to quantitate new bone formation induced by the WISH tumor, we examined the effects of ET-1 overexpression and endothelin receptor antagonists on the osteoblastic response.
Results. WISH, a human tumor cell line derived from amnion, produces ET-1 mRNA and protein and induces abundant new bone formation and splenomegaly in vivo. Stable transfection of WISH with an ET-1 overexpression cDNA construct produced clones that secreted 18-fold more bioactive ET-1 than vector-only controls. After 14 days of growth in the lower leg of nu/nu mice, ET-1 overexpressing tumors produced significantly more new bone than vector-only controls. Conversely, areas of new bone formation were significantly less in animals treated with a selective endothelin A (ETA) receptor antagonist A127722.
Conclusions. The activity of ET-1 in this osteoblastic model provides a unique target for therapy.
Le texte complet de cet article est disponible en PDF.Plan
 | This work was supported by the NIH Prostate Cancer Specialized Programs of Research Excellence CA 58236, CaP CURE, and Abbott Laboratories, Inc. |
Vol 53 - N° 5
P. 1063-1069 - mai 1999 Retour au numéro
Article précédent
- In vitro bactericidal activities of beta-lactamases, amikacin, and fluoroquinolones against pseudomonas aeruginosa biofilm in artificial urine
- Toshihiro Goto, Yasuhiko Nakame, Morio Nishida, Yoshitada Ohi
- Correspondence
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?