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• W2080436420 abstract "Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, ILInterleukin-11 (IL-11) is a member of the IL-6 cytokine family, which mediate signaling via a common signal-transducing gp130 component and a cytokine-specific subunit (IL-11Rβ). Upon binding to the IL-11Rα, a signaling cascade activates several pathways, including JAK kinases, STAT transcription factors (STAT3 and STAT1), MAPK, src-family kinases and PI3K. IL-11 has been implicated in experimental models of chronic inflammation and associated tumorigenesis. Oncomine analysis of publicly available microarray data from patient biopsies showed that IL-11Rα mRNA is expressed in several sarcomas and not in the matched normal tissue counterparts. Surgical resection and cytotoxic chemotherapy are the standard of care for most locally advanced and metastatic sarcomas, the identification of new markers and the development of targeted therapies are needed to increase long-term survival of these patients. Previous studies demonstrated IL-11Rα is expressed in human primary and metastatic osteosarcomas but not in normal bone, suggesting that IL-11Rα is a potential target for sarcoma therapy. We analyzed a panel of 45 human sarcoma cell lines for the expression of IL-11Rα and IL-11. Interestingly, IL-11Rα protein is expressed at high levels in the majority of cell lines examined. In addition, we found that nearly all osteosarcoma, rhabdomyosarcoma, fibrosarcoma and Ewing sarcoma cell lines express high constitutive levels of IL-11 mRNA, indicating that IL-11 autocrine signaling may play a role in these tumor types. Two lentiviral vectors, used for the delivery of shRNA targeting IL-11 in HT-1080, produced an 80-90% decrease in IL-11 mRNA expression when compared to the luciferase control shRNA; however, IL-11 mRNA levels remained significantly high in HT1080 knock-down cells when compared to the constitutive levels of non sarcoma cancer types. Decreasing levels of IL-11 in HT-1080 resulted in a 50% inhibition of cell growth, demonstrating that IL-11 has a role in cell proliferation. Further experiments aimed to assess the expression of IL-11 and IL-11Rβ in xenografts and to explore the role of IL-11 in sarcoma pathogenesis, propagation and response to therapy are ongoing. These data suggest that neutralization of IL-11 or IL-11Rα may be a potential target for the development of cancer therapeutics for sarcomas. Funded by NCI Contract No. HHSN261200800001E.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 890. doi:1538-7445.AM2012-890" @default.
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• W2080436420 date "2012-04-15" @default.
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• W2080436420 title "Abstract 890: Interleukin 11: A novel therapeutic target in IL-11Rα expressing sarcomas" @default.
• W2080436420 doi "https://doi.org/10.1158/1538-7445.am2012-890" @default.
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