Session: SUN 199-233-Bone Biology
Poster Board SUN-221
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
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