IL-11Rα is an important cytokine receptor that links oxidative stress and compensatory proliferation. Mounting evidence has demonstrated that IL-11Rα regulates autoimmune demyelination and the invasion and proliferation of cancer cells, making it an important therapeutic target for molecular targeted therapy. Moreover, overexpression of IL-11Rα indicates a poor long-term prognosis in cancer patients. However, the expression status and its potential as a biomarker for diagnosis, tumor imaging, and prognosis in osteosarcoma remain to be determined. We report here that IL-11Rα is highly expressed in osteosarcoma and near-infrared (NIR)-labeled IL-11Rα imaging agent could detect osteosarcoma in mouse tumor xenografts. In a panel of human osteosarcoma specimens, IL-11Rα protein was positively stained in most cases by immunohistochemistry. Western blot analysis and flow cytometry showed that IL-11Rα was overexpressed in osteosarcoma SOSP-9607 cells. Cell-binding assay demonstrated specific binding of the IL-11Rα targeted imaging agent to osteosarcoma SOSP-9607 cells in vitro. In addition, administration of an IL-11Rα targeted imaging agent in a nude mice orthotopic model resulted in selective accumulation of NIR fluorescent signals in the bone tumor as well as several metabolic organs. These results indicate that IL-11Rα is a potential target for the development of molecular targeted therapy and noninvasive tumor imaging in human osteosarcoma. Furthermore, NIR-labeled IL-11Rα imaging agent is a promising lead for the development of a tumor in vivo imaging method at the molecular level in the management of human osteosarcoma.
Interleukin-11 receptor α Human osteosarcoma Molecular imaging NIR Molecular target
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This work is supported by the grant from the National Natural Science Foundation of China (No. 30873027, 30973409). We would like to thank Mingjun Guo, Haien Zhao, and Guangyi Zhao for their excellent technical assistance and helpful discussions.
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