Neuroblastoma prognosis is dependent on both the differentiation state and stromal content of the tumor. Neuroblastoma tumor stroma is thought to suppress neuroblast growth via release of soluble differentiating factors. Here, we identified critical growth-limiting components of the differentiating stroma secretome and designed a potential therapeutic strategy based on their central mechanism of action. We demonstrated that expression of heparan sulfate proteoglycans (HSPGs), including TβRIII, GPC1, GPC3, SDC3, and SDC4, is low in neuroblasts and high in the Schwannian stroma. Evaluation of neuroblastoma patient microarray data revealed an association between
Erik H. Knelson, Angela L. Gaviglio, Jasmine C. Nee, Mark D. Starr, Andrew B. Nixon, Stephen G. Marcus, Gerard C. Blobe
sHSPGs released from the stroma promote neuroblast differentiation.