Expression of type I interferon receptor in solid tumors of childhood.
Interferon alpha (IFN alpha) is used as an antineoplastic agent, both in hematopoietic malignancies and in solid tumors, because of its immunomodulatory action and direct antitumor activity. IFN alpha binds to specific cell-surface receptors that mediate its biologic activity. We studied the expression of IFN alpha receptors in pediatric solid tumors by use of the monoclonal antibody IFNaR3, which specifically recognizes the alpha subunit of the IFN Type I receptor. In three cell lines derived from those tumors, we determined the structure of the receptors by affinity cross-linking and immunoprecipitation techniques, and we determined their ability to mediate an antiproliferative effect. All of the tumor specimens studied by immunocytochemical analysis, including neuroblastomas, primitive neuroectodermal tumors, and rhabdomyosarcomas, stained positive for the IFN alpha receptor antibody, although in some cases immunoreactivity was weak. The three cell lines, derived from a neuroblastoma, a primitive neuroectodermal tumor, and a Ewing's sarcoma, respectively, showed the same pattern of IFN alpha receptor expression, both by affinity crosslinking and immunoprecipitation assays. Treatment with IFN alpha of those cell lines induces growth inhibition in vitro. These results suggest that IFN Type I receptor might be expressed in most solid tumors of childhood and that its structure is identical to the receptor expressed by the majority of hematologic malignancies.
Rosolen
A
A
Department of Pediatrics, University of Padua, Italy. rosolen@child.pedi.unipd.it
Todesco
A
A
Colamonici
O R
OR
Basso
G
G
Frascella
E
E
D000293:Adolescent; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D016898:Interferon-alpha / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D018242:Neuroectodermal Tumors, Primitive / Q000378:metabolism* / Q000473:pathology; D017471:Receptors, Interferon / Q000096:biosynthesis* / Q000378:metabolism; D012208:Rhabdomyosarcoma / Q000378:metabolism* / Q000473:pathology; D012509:Sarcoma / Q000378:metabolism / Q000473:pathology; D012512:Sarcoma, Ewing / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
D016898:Interferon-alpha; D017471:Receptors, Interferon