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: Tao Liu, Qiong Ma, Yinglong Zhang, Shi Ke, Kang Yan, Xiang Chen, Yanhua Wen, Qingyu Fan, Xiuchun Qiu
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 36 Issue 4 Pg. 2369-75 (Apr 2015) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 25524575 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• IL11RA protein, human
• Interleukin-11 Receptor alpha Subunit

Topics

• Animals
• Bone Neoplasms (genetics, pathology)
• Cell Line, Tumor
• Cell Tracking
• Flow Cytometry
• Gene Expression Regulation, Neoplastic
• Humans
• Interleukin-11 Receptor alpha Subunit (biosynthesis, genetics)
• Mice
• Molecular Imaging
• Molecular Targeted Therapy
• Osteosarcoma (genetics, pathology)
• Xenograft Model Antitumor Assays