Abstract 1261: Targeting IL-11Rα inhibits osteosarcoma pulmonary metastasis in an orthotopic xenograft mouse model

Abstract Osteosarcoma is the most common primary tumor of bones. In the past three decades treatment paradigms and survival rates have not improved. While osteosarcoma clinical phenotype has been well characterized, the underlying tumor molecular biology remains unclear. We have previously demonstrated that IL-11Rα is overexpressed in primary and metastatic osteosarcoma. Recently investigators identified that IL-11 and IL-11Rα play a role in the development of metastasis in breast and gastrointestinal cancer. However the role of IL-11/IL-11Rα signaling in osteosarcoma is unknown. Using in vitro and in vivo osteosarcoma models we investigated the role of IL-11/IL-11Rα in osteosarcoma metastasis. The purpose of our study is to determine the effect of the knockdown of IL-11Rα in osteosarcoma. We stably knocked down IL-11Rα expression in a highly metastatic osteosarcoma cell line, using a lentiviral short hair-pin (shRNA) based approach. Knockdown of IL-11Rα led to inhibition of STAT-3(Tyr705) protein phosphorylation, cell growth, migration, invasion and colony formation in vitro. To determine the role of IL-11Rα in osteosarcoma tumorigeniesis and metastasis, we used an orthotopic metastatic model. In this model, mice injected with KRIB-IL-11Rα shRNA cells developed significantly less metastasis than control mice injected with KRIB control shRNA (P<0.01). The relevance of our data to human conditions was studied by immunohistochemical staining of IL-11Rα protein in human osteosarcoma biopsy samples containing primary tumor and lesions, significant difference (p<0.01) in expression distribution between primary and metastatic osteosarcoma lesions and a trend toward an impact on survival was noted. In conclusion, we showed that IL-11Rα plays an important role in the development of metastasis in osteosarcoma and blockade of this axis may inhibit the formation of metastasis and may provide an excellent target for the treatment of osteosarcoma. Citation Format: Valerae O. Lewis, Eswaran Devarajan, Dennis PM Hughes. Targeting IL-11Rα inhibits osteosarcoma pulmonary metastasis in an orthotopic xenograft mouse model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1261. doi:10.1158/1538-7445.AM2014-1261