The interleukin-11 receptor alpha as a candidate ligand-directed target in osteosarcoma: consistent data from cell lines, orthotopic models, and human tumor samples.

Abstract

The interleukin-11 receptor alpha (IL-11Ralpha) is a functional target in bone metastasis. However, its role in primary bone tumors has not been established. As such, here, we evaluated IL-11Ralpha as a candidate target in primary and metastatic human osteosarcoma. First, in an orthotopic mouse model, we showed that IL-11Ralpha 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-11Ralpha-targeting phage displaying the cyclic nonapeptide CGRRAGGSC resulted in strong and selective accumulation of IL-11Ralpha-homing phage particles in the osteosarcoma but not in several control organs. Finally, IL-11Ralpha 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-11Ralpha 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.

• Authors: Valerae O Lewis, Michael G Ozawa, Michael T Deavers, Guiying Wang, Tomo Shintani, Wadih Arap, Renata Pasqualini
• Journal: Cancer research (Cancer Res) Vol. 69 Issue 5 Pg. 1995-9 (Mar 01 2009) ISSN: 1538-7445 [Electronic] United States
• PMID: 19244100 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

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

Topics

• Animals
• Bone Neoplasms (chemistry, pathology)
• Cell Line, Tumor
• Humans
• Interleukin-11 Receptor alpha Subunit (analysis)
• Ligands
• Lung Neoplasms (chemistry, secondary)
• Male
• Mice
• Osteosarcoma (chemistry, pathology)