The Role of the Serotonergic System in Canine Osteosarcoma

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 199-233-Bone Biology
Basic/Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-221
Shay Bracha*1, Austin Viall1, Cheri Peyton Goodall2 and Patrick Everett Chappell1
1Oregon State University College of Veterinary Medicine, Corvallis, OR, 2Oregon State University, College of Veterinary Medicine, Corvallis, OR
The serotonergic system plays a major role in osteoblast proliferation and bone remodeling. Five-hydroxytryptamine (5HT) can both stimulate and repress osteoblast proliferation, dependent upon what receptor isoforms are present. The 5HT receptor 2A (5HT2AR) has been shown to influence cell proliferation upon agonist binding via phosphorylation of ERK, whereas serotonin can suppress osteoblast proliferation by inhibiting CREB phosphorylation, mediated by 5HT-1B receptor (5HT1BR).

While the role of serotonin in normal bone remodeling is well-characterized, how these separate signaling pathways are affected in bone cancer is not clear. We have examined the expression and function of these two key receptors in canine osteosarcoma cell lines, which have proven to be a strong model for the disease in people. Our results reveal the expression of both 5HT2AR and 5HT1BR in each of the lines studied. Challenging the cells with increasing concentrations of serotonin increased cell viability, accompanied by ERK and CREB phosphorylation. When the cells were treated with serotonin and increasing concentrations of Ritanserin, a 5HT2AR inhibitor, osteosarcoma cells showed a decreased viability, as well as ERK de-phosphorylation, demonstrating the role of 5HT2AR in stimulating proliferation in osteosarcoma. Antagonizing 5HT1BR (via SB224289) in osteosarcoma cells pre-treated with serotonin abolished the phosphorylation of CREB and decreased cell viability in a dose dependent manner. While in normal osteoblasts serotonin may suppress cell viability via a dominant 5HT1BR, the opposite appears true for malignant cells.  Based on the apparently significant role of 5HT2A and 5HT1B in osteosarcomas, we propose that these receptors may serve as novel targets for the treatment of osteosarcoma in both veterinary and human clinical contexts.

Nothing to Disclose: SB, AV, CPG, PEC

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: College of Veterinary Medicine Internal Grant awarded to SB