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

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