Insulin-like growth factor I expression by tumors of neuroectodermal origin with the t(11;22) chromosomal translocation. A potential autocrine growth factor.

Expression ofinsulin-like growth factor I(IGF-I) mRNA by sometumorcell lines ofneuroectodermal origin hasbeendescribed. Tofurther explore thesignificance ofIGF-I mRNA expression inthese tumors, amoreextensive analysis wasperformed. Most(9of10)neuroectodermal tumorcell lines witha t(11;22) translocation (primitive neuroectodermal tumor IPNETI, Ewing's sarcoma, esthesioneuroblastoma) expressed IGF-ImRNA,whereas 0of15cell lines without thetranslocation (PNET, neuroblastoma) expressed IGF-I. Furthermore, inasmuch asallneuroblastoma (12of12)cell lines examined expressed IGF-II RNA,thepattern ofIGFexpression could distinguish between these closely related tumors. CHP-100, a PNETcell line withthet(11;22) translocation, wasshownto secrete bothIGF-Iprotein andanIGFbinding protein, IGFBP-2. Thiscell line also expressed thetype IIGFreceptor mRNA,andblockade ofthis receptor byamonoclonal antibody(aIR3) inhibited serum-free growth. Thesedatademonstrate that IGF-I expression isaproperty ofneuroectodermal tumors with at(l 1;22) translocation andthat interruption ofan IGF-I autocrine loopinhibits thegrowth ofthese tumorcells. (J.Clin. Invest. 1990. 86:1806-1814.) Keywords: Ewing's sarcoma *insulin-like growth factor binding protein 2*insulin-like growth factor II*neuroblastoma *typeIinsulin-like growth factor receptor