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Published in: Tumor Biology 4/2015

01-04-2015 | Research Article

Interleukin-11 receptor α is overexpressed in human osteosarcoma, and near-infrared-labeled IL-11Rα imaging agent could detect osteosarcoma in mouse tumor xenografts

Authors: Tao Liu, Qiong Ma, Yinglong Zhang, Shi Ke, Kang Yan, Xiang Chen, Yanhua Wen, Qingyu Fan, Xiuchun Qiu

Published in: Tumor Biology | Issue 4/2015

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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.
Literature
1.
go back to reference Mirabello L, Troisi RJ, Savage SA. Osteosarcoma incidence and survival rates from 1973 to 2004: data from the surveillance, epidemiology, and end results program. Cancer. 2009;115:1531–43.CrossRefPubMedPubMedCentral Mirabello L, Troisi RJ, Savage SA. Osteosarcoma incidence and survival rates from 1973 to 2004: data from the surveillance, epidemiology, and end results program. Cancer. 2009;115:1531–43.CrossRefPubMedPubMedCentral
2.
go back to reference Bakhshi S, Radhakrishnan V. Prognostic markers in osteosarcoma. Expert Rev Anticancer Ther. 2010;10:271–87.CrossRefPubMed Bakhshi S, Radhakrishnan V. Prognostic markers in osteosarcoma. Expert Rev Anticancer Ther. 2010;10:271–87.CrossRefPubMed
3.
go back to reference Posthuma DeBoer J, Witlox MA, Kaspers GJ, van Royen BJ. Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature. Clin Exp Metastasis. 2011;28:493–503.CrossRef Posthuma DeBoer J, Witlox MA, Kaspers GJ, van Royen BJ. Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature. Clin Exp Metastasis. 2011;28:493–503.CrossRef
4.
go back to reference Luetke A, Meyers PA, Lewis I, et al. Osteosarcoma treatment—where do we stand? A state of the art review. Cancer Treat Rev. 2014;40:523–32.CrossRefPubMed Luetke A, Meyers PA, Lewis I, et al. Osteosarcoma treatment—where do we stand? A state of the art review. Cancer Treat Rev. 2014;40:523–32.CrossRefPubMed
5.
go back to reference Huang G, Ling Y, Laurence JN, et al. Genetically modified T cells targeting interleukin-11 receptorα-Chain kill human osteosarcoma cells and induce the regression of established osteosarcoma lung metastases. Cancer Res. 2012;72:271–81.CrossRefPubMed Huang G, Ling Y, Laurence JN, et al. Genetically modified T cells targeting interleukin-11 receptorα-Chain kill human osteosarcoma cells and induce the regression of established osteosarcoma lung metastases. Cancer Res. 2012;72:271–81.CrossRefPubMed
6.
go back to reference Cho N, Nguyen DH, Satkunendrarajah K, et al. Evaluating the role of IL-11, a novel cytokine in the IL-6 family, in a mouse model of spinal cord injury. J Neuroinflammation. 2012;9:134–56.CrossRefPubMedPubMedCentral Cho N, Nguyen DH, Satkunendrarajah K, et al. Evaluating the role of IL-11, a novel cytokine in the IL-6 family, in a mouse model of spinal cord injury. J Neuroinflammation. 2012;9:134–56.CrossRefPubMedPubMedCentral
7.
go back to reference Berlin O, Samid D, Donthineni-Rao R, et al. Development of a novel spontaneous metastasis model of human osteosarcoma transplanted orthotopically into bone of athymic mice. Cancer Res. 1993;53:4890–5.PubMed Berlin O, Samid D, Donthineni-Rao R, et al. Development of a novel spontaneous metastasis model of human osteosarcoma transplanted orthotopically into bone of athymic mice. Cancer Res. 1993;53:4890–5.PubMed
8.
go back to reference Khanna C, Prehn J, Yeung C, et al. An orthotopic model of murine osteosarcoma with clonally related variants differing in pulmonary metastatic potential. Clin Exp Metastasis. 2000;18:261–71.CrossRefPubMed Khanna C, Prehn J, Yeung C, et al. An orthotopic model of murine osteosarcoma with clonally related variants differing in pulmonary metastatic potential. Clin Exp Metastasis. 2000;18:261–71.CrossRefPubMed
9.
go back to reference Chen X, Yang TT, Wang W, et al. Establishment and characterization of human osteosarcoma cell lines with different pulmonary metastatic potentials. Cytotechnology. 2009;61:37–44.CrossRefPubMedPubMedCentral Chen X, Yang TT, Wang W, et al. Establishment and characterization of human osteosarcoma cell lines with different pulmonary metastatic potentials. Cytotechnology. 2009;61:37–44.CrossRefPubMedPubMedCentral
10.
go back to reference Wang W, Ke S, Kwon S, et al. A new optical and nuclear dual-labeled imaging agent targeting interleukin 11 receptor alpha-chain. Bioconjug Chem. 2007;18:397–402.CrossRefPubMed Wang W, Ke S, Kwon S, et al. A new optical and nuclear dual-labeled imaging agent targeting interleukin 11 receptor alpha-chain. Bioconjug Chem. 2007;18:397–402.CrossRefPubMed
11.
go back to reference Kang Y, Siegel PM, Shu W, et al. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell. 2003;3:537–49.CrossRefPubMed Kang Y, Siegel PM, Shu W, et al. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell. 2003;3:537–49.CrossRefPubMed
12.
go back to reference Kolb EA, Gorlick R, Houghton PJ, et al. Initial testing (stage 1) of a monoclonal antibody (SCH 717454) against the IGF-1 receptor by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008;50:1190–7.CrossRefPubMed Kolb EA, Gorlick R, Houghton PJ, et al. Initial testing (stage 1) of a monoclonal antibody (SCH 717454) against the IGF-1 receptor by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008;50:1190–7.CrossRefPubMed
13.
go back to reference Kolb EA, Kamara D, Zhang W, et al. R1507, a fully human mono-clonal antibody targeting IGF-1R, is effective alone and in combination with rapamycin in inhibiting growth of osteosarcoma xenografts. Pediatr Blood Cancer. 2010;55:67–75.CrossRefPubMed Kolb EA, Kamara D, Zhang W, et al. R1507, a fully human mono-clonal antibody targeting IGF-1R, is effective alone and in combination with rapamycin in inhibiting growth of osteosarcoma xenografts. Pediatr Blood Cancer. 2010;55:67–75.CrossRefPubMed
14.
go back to reference Ahmed N, Salsman VS, Yvon E, et al. Immunotherapy for osteosarcoma: genetic modification of T cells overcomes low levels of tumor antigen expression. Mol Ther. 2009;17:1779–87.CrossRefPubMedPubMedCentral Ahmed N, Salsman VS, Yvon E, et al. Immunotherapy for osteosarcoma: genetic modification of T cells overcomes low levels of tumor antigen expression. Mol Ther. 2009;17:1779–87.CrossRefPubMedPubMedCentral
Metadata
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
Authors
Tao Liu
Qiong Ma
Yinglong Zhang
Shi Ke
Kang Yan
Xiang Chen
Yanhua Wen
Qingyu Fan
Xiuchun Qiu
Publication date
01-04-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 4/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2844-6

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