title: Interleukin-11 receptor α is overexpressed in human osteosarcoma, and near-infrared-labeled IL-11Rα imaging agent could detect osteosarcoma in mouse tumor xenografts.
abstract: 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.
authors.affiliation: Department of Orthopedic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shanxi, 710038, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Qiong
authors.initials: Q
authors.lastname: Ma
authors.forename: Yinglong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shi
authors.initials: S
authors.lastname: Ke
authors.forename: Kang
authors.initials: K
authors.lastname: Yan
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Wen
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Fan
authors.forename: Xiuchun
authors.initials: X
authors.lastname: Qiu
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D058948:Cell Tracking; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053703:Interleukin-11 Receptor alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D057054:Molecular Imaging; D058990:Molecular Targeted Therapy; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: C508428:IL11RA protein, human; D053703:Interleukin-11 Receptor alpha Subunit