NTRK1/TrkA expression is a potential regulator of neuroblastoma cross-talk with the schwannian stroma

Schwann cells (SC) are the predominant morphological feature of neuroblastomas (NB) with good prognosis. High-level NTRK1/TrkA expression, which is known to mediate tumor cell differentiation, is characteristic of this NB subgroup. We hypothesized that Schwannian stromal development and neuroblastic differentiation is based on bidirectional interaction of NB and SC. Reanalysis of microarray data from SY5Y NB cells stably transfected with NTRK1, NTRK2 or the empty vector revealed that upregulation of genes influencing motility and growth of SC is restricted to NTRK1-positive cells. Incubation of primary SC with supernatants of NTRK1-expressing NB cells significantly enhanced SC proliferation and migration. SC-conditioned medium also induced differentiation of NTRK1-expressing cells. Finally, NTRK1 induction in NB xenografts mixed with primary SC significantly reduced tumor growth in vivo. In addition to effects on angiogenesis, immunogenicity and apoptosis, NTRK1 expression in NB might attract adjacent SC that then induce neuroblastic differentiation by secreting the NTRK1-specific ligand, nerve growth factor, and thus, contributing to a mature and less malignant NB phenotype.