The interleukin-11 receptor alpha as a candidate ligand-directed target in osteosarcoma: consistent data from cell lines, orthotopic models, and human tumor samples.
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.
Lewis
Valerae O
VO
Section of Orthopedic Oncology, Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. volewis@mdanderson.org
Ozawa
Michael G
MG
Deavers
Michael T
MT
Wang
Guiying
G
Shintani
Tomo
T
Arap
Wadih
W
Pasqualini
Renata
R
D000818:Animals; D001859:Bone Neoplasms / Q000737:chemistry* / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D053703:Interleukin-11 Receptor alpha Subunit / Q000032:analysis*; D008024:Ligands; D008175:Lung Neoplasms / Q000737:chemistry / Q000556:secondary; D008297:Male; D051379:Mice; D012516:Osteosarcoma / Q000737:chemistry* / Q000473:pathology
C508428:IL11RA protein, human; D053703:Interleukin-11 Receptor alpha Subunit; D008024:Ligands