Schwann cell-conditioned medium inhibits angiogenesis in vitro and in vivo

Background. Neuroblastomas are biologically heterogeneous tumors that consi st of two main cell populations: neurobtastic/ganglionic cells and Schwann cells. The amount of Schwannian stroma strongly impacts prognosis. Low tumo r vascularity, localized stage, and favorable outcome are associated with t umors that are Schwannian stroma-rich/siroma-dominant. Procedure. To invest igate if Schwann cells play a role in inhibiting angiogenesis in neuroblast oma tumors, we examined the ability of human Schwann cell-conditioned mediu m to affect bFGF- and VEGF-induced endothelial cell proliferation and migra tion, and in vivo angiogenesis. Results. Schwann cell-conditioned medium si gnificantly inhibited bFCF- and VEGF-induced endothelial cell proliferation and migration. This effect appears to be specific for endothelial cells as smooth muscle cell and fibroblast proliferation were not inhibited by this medium. Schwann cell-conditioned medium also inhibited in vivo angiogenesi s in rat corneal assays. Conclusions. Schwann cells produce a potent inhibi tor(s) of angiogenesis that may be responsible for the row level of vascula rity and more benign clinical behavior of Schwannian stroma-rich/stroma-dom inant neuroblastoma tumors. Studies to identify the inhibitor(s) are ongoin g. (C) 2000 Wiley-Liss, Inc.