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The Interleukin-11 Receptor as a Candidate Ligand-Directed Target in Osteosarcoma: Consistent Data from Cell Lines, Orthotopic Models, and Human Tumor Samples

¹ Section of Orthopedic Oncology, Department of Surgical Oncology, ² David H. Koch Center, and Departments of ³ Pathology and ⁴ Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Valerae O. Lewis, Wadih Arap, or Renata Pasqualini, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-792-3873; Fax: 713-745-2999; E-mail: volewis{at}mdanderson.org, warap{at}mdanderson.org, or rpasqualini{at}mdanderson.org.

Key Words: phage display • bone tumors • targeted delivery • IL-11 • metastasis

The interleukin-11 receptor (IL-11R) is a functional target in bone metastasis. However, its role in primary bone tumors has not been established. As such, here, we evaluated IL-11R as a candidate target in primary and metastatic human osteosarcoma. First, in an orthotopic mouse model, we showed that IL-11R protein is markedly expressed in primary osseus and pulmonary metastatic osteosarcoma but absent from control normal tibia and lung. Moreover, systemic administration of an IL-11R–targeting phage displaying the cyclic nonapeptide CGRRAGGSC resulted in strong and selective accumulation of IL-11R–homing phage particles in the osteosarcoma but not in several control organs. Finally, IL-11R expression in a large panel of human primary and metastatic osteosarcoma samples was remarkably consistent with the observations in the orthotopic mouse model. These data establish IL-11R as a candidate target in human osteosarcoma and provide leads for the development of novel imaging and therapeutic agents for the management of this malignant tumor. [Cancer Res 2009;69(5):1995–9]