TY - JOUR
T1 - The lnterleukin-11 receptor a as a candidate ligand-directed target in osteosarcoma
T2 - Consistent data from cell lines, orthotopic models, and human tumor samples
AU - Lewis, Valerae O.
AU - Ozawa, Michael G.
AU - Deavers, Michael T.
AU - Wang, Guiying
AU - Shintani, Tomo
AU - Arap, Wadih
AU - Pasqualini, Renata
PY - 2009/3/1
Y1 - 2009/3/1
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-08-4845
DO - 10.1158/0008-5472.CAN-08-4845
M3 - Article
C2 - 19244100
AN - SCOPUS:62449095801
SN - 0008-5472
VL - 69
SP - 1995
EP - 1999
JO - Cancer Research
JF - Cancer Research
IS - 5
ER -