Neuroblastoma cells provoke Schwann cell proliferation in vitro

Background. A subset of human neuroblastomas (NBs) has the capacity to matu re completely, imitating sympathetic ganglia. Previously, we showed that th e neuronal population in spontaneously maturing NBs usually has a near-trip loid DNA content without 1p deletions, and we concluded that the constantly diploid Schwann cells (SCs) do not belong to the neoplastic component of t hese rumours. We therefore hypothesised that NE cells are able to stimulate SC proliferation, and that SCs trigger NE differentiation. Procedure. We p erformed in vitro experiments to test this model and to test whether SCs ca n also influence the growth of aggressive NBs. Human SCs were cocultivated with NE tumours and cell lines, and were harvested after defined time inter vals. Proliferative activity of the SCs and the NE cells was determined by visualisation of 5-bromo-2'-deoxyuridine (BrdU) incorporation or Ki-67 stai ning. Neurite outgrowth and neurofilament (NF) expression were analysed imm unocytochemically and apoptotic rate was determined by a terminal deoxynucl eotidyl transferase-mediated dUTP-X fluorescein nick end labelling (TUNEL) assay. Results. Human NE tumours or cell lines unequivocally increased the proliferation of SCs in vitro. In cocultivated NE cells, the proliferative activity was not altered in the first days of cocultivation, although neuri te outgrowth and NF expression were enhanced. However, after 10 days, the m itotic rate of neuroblastic cells decreased and the apoptotic rate showed a marked increase. Conclusions. The results of the cocultivation experiments provide an experimental hint that the in vivo growth of SCs in NBs is caus ed by the neoplastic neuroblasts, and they also indicate that cells from pe ripheral nerves can influence the growth of aggressive NE cells if cocultiv ated. Med. Pediatr. Oncol. 36:163-168, 2001. (C) 2001 Wiley-Liss, Inc.