B623 IL-17 Promotes Tumor cell Growth and Survival, and Inhibits Immune Function in Myeloma

Autor: Mariateresa Fulciniti, Nithya Prabhala, Dheeraj Pelluru, YT Tai, K Lefkimmiatis, Puru Nanjappa, KC Anderson, John F. Daley, Rao Prabhala, C Mitsiaties, NC Munshi, Y. A. Efebera
Rok vydání: 2009
Předmět:
Zdroj: Clinical Lymphoma and Myeloma. 9:S159
ISSN: 1557-9190
DOI: 10.1016/s1557-9190(11)70795-8
Popis: Then focused on the RTK’s which were shown to be upregulated in WM and tested the effect of TKI-258 effect on their activity. Moreover, we tested the effect of TKI-258 survival, proliferation, and apoptosis of WM cells, and its effect of different signaling pathways in WM. Results: We found that epidermal growth factor receptor (EGF-R), ephrin receptor (Eph-R) and receptor tyrosine kinase–like orphan receptor 1 (ROR-1) were highly activated in WM patients compared to normal subjects (5, 10, and 14-fold increase, respectively), and were found to be upregulated also in BCWM1. TKI-258 reduced the activity of EGF-R and Eph-R, but not ROR1. Moreover, TKI-258 induced cytotoxicity, prevented proliferation and induced apoptosis in WM cells in a dose dependent manner with IC50 of 500-800 nM. Moreover, it was shown to induce cleavage of PARP, caspase-3 and caspase-9, and also reduced phosphorylations of ERK1/2. Conclusion: We identified two novel therapeutic targets for WM; EGF-R and Eph-R, and identified Eph-R as a novel target of TKI-258. Moreover, TKI-258 reduced WM progression in vitro, and we are now testing the effect of TKI-258 on WM progression in vitro and alone and in combination with other drugs.
Databáze: OpenAIRE
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