The angiogenic factor midkine is aberrantly expressed in NF1-deficient Schwann cells and is a mitogen for neurofibroma-derived cells.

摘要: Loss of the tumor suppressor gene NF1 in neurofibromatosis type 1 (NF1) contributes to development a variety tumors, including malignant peripheral nerve sheath tumors (MPNST) and benign neurofibromas. Of different cell types found neurofibromas, Schwann cells usually provide between 40 80%, are thought be critical for growth. Here we describe identification growth factors that upregulated NF1-/- mouse potential regulators angiogenesis Basic fibroblast factor (FGF-2), platelet-derived (PDGF) midkine (MK) were induced by loss neurofibromin MK was further characterized. human schwannomas, various nervous system associated with or NF2; showed an expression pattern overlapping but distinct from its homolog pleiotrophin (PTN). Immunohistochemistry revealed S-100 positive dermal plexiform endothelial blood vessels, not normal vessels. Furthermore, demonstrated potent mitogenic activity systemic brain vitro stimulated proliferation soft agar colony formation MPNST derived S100 fibroblastoid neurofibroma. The data support possible central role as mediator neurofibroma NF1. Oncogene (2001) 20, 97 - 105.