© 2001 by Society
© 2001 by the Society forNeuro-Oncology
Expression and localization of scatter factor/hepatocyte growth factor inhuman astrocytomas
Departments of Neurosurgery (P.K., S.M., R.F., M.W.)and Neuropathology (D.S., K.L.), University HospitalHamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; and Institute of Pathology, University of Cologne,Joseph-Stelzmann-Strasse 9, 50931 Cologne, Germany (P.S.)
2 Address correspondence and reprint requests to Katrin Lamszus, Department ofNeuropathology, University Hospital Eppendorf, Martinistrasse 52, 20246Hamburg, Germany.
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Abstract |
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Scatter factor/hepatocyte growth factor (SF/HGF) is a pleiotropic cytokinethat has been implicated in glioma invasion and angiogenesis. The SF/HGFreceptor, MET, has been found to be expressed in neoplastic astrocytes as wellas in endothelial cells of the tumor vasculature. Both SF/HGF and METexpression have also been described to correlate with the malignancy grade ofhuman gliomas. However, most glioblastoma cell lines lack SF/HGF expression,raising the question of the cellular origin of SF/HGF in vivo. Using in situhybridization, we analyzed glioblastomas, anaplastic astrocytomas, diffuseastrocytomas, pilocytic astrocytomas, and normal brain for the expression ofSF/HGF mRNA. We detected strong SF/HGF expression by the majority of the tumorcells and by vascular endothelial cells in all glioblastoma specimensanalyzed. Combined use of in situ hybridization with fluorescenceimmunohistochemistry confirmed the astrocytic origin of the SF/HGF-expressingcells. In contrast, CD68-immunoreactive microglia/macrophages, as well asvascular smooth muscle cells reactive to -smooth muscle actin, lacked SF/HGFexpression. In anaplastic, diffuse, and pilocytic astrocytomas, SF/HGFexpression was confined to a subset of tumor cells, and signals were lessintense than in glioblasto mas. In addition, we detected SF/HGF mRNA incortical neurons. SF/HGF expression was not up regulated around necroses or attumor margins. MET immunoreactivity was observed in GFAP-expressing astrocytictumor cells and endothelial cells as well as in a subset ofmicroglia/macrophages. We conclude that in vivo, both autocrine and paracrinestimulation of tumor cells and endothelium through the SF/HGF-MET system arelikely to contribute to tumor invasion and angiogenesis. Lack of SF/HGFexpression by most cultured glioblastoma cells is not representative of the invivo situation and most likely represents a culture artifact.
Received August 8, 2000; Accepted November 2, 2000
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