PMID- 10232541 OWN - NLM STAT- MEDLINE DCOM- 19990624 LR - 20220223 IS - 0148-396X (Print) IS - 0148-396X (Linking) VI - 44 IP - 5 DP - 1999 May TI - In vitro modulation of microglia motility by glioma cells is mediated by hepatocyte growth factor/scatter factor. PG - 1077-82; discussion 1082-3 AB - OBJECTIVE: Considered as immune effector cells of the central nervous system, microglia represent a major component of the inflammatory cells found in malignant gliomas. Although their role in brain tumor biology is unclear, accumulation of microglia in malignant brain tumors may be mediated through active secretion of cytokines by glioma cells. Because hepatocyte growth factor/scatter factor (HGF/SF) has been shown to modulate glioma motility through an autocrine mechanism, and because microglia have been reported to express the HGF/SF receptor Met, we hypothesized that microglia recruitment by gliomas may also occur through the secretion of HGF/SF. METHODS: The effect of glioma cells in augmenting BV-2 murine microglia motility was studied by using an in vitro Boyden chamber migration assay. To determine the chemokines involved in microglia migration, neutralizing monoclonal antibodies against monocyte chemotactic protein-1 and HGF/SF were tested. Immunoblotting was used to check for the expression of HGF/SF by glioma cells, and the expression of Met by BV-2 cells was examined by flow cytometry. RESULTS: BV-2 migration was noted within 7 hours of incubation with both human (U251 MG and U373 MG) and murine (GL261) glioma cell lines. This migration corresponded to HGF/SF secretion by glioma cells and was completely inhibited by neutralizing monoclonal antibody against HGF/SF, but not monocyte chemotactic protein-1. Exposure of BV-2 cells to recombinant HGF/SF, but not monocyte chemotactic protein-1, resulted in their migration and down-regulation of Met in a dose-dependent fashion. CONCLUSION: HGF/SF, which plays a role in glioma motility and mitogenesis, may also act as a chemokine for microglia and may be responsible for the microglia infiltration in malignant gliomas. This active recruitment of microglia may play an important role in glioma biology. FAU - Badie, B AU - Badie B AD - Department of Neurological Surgery, University of Wisconsin School of Medicine, Madison, USA. FAU - Schartner, J AU - Schartner J FAU - Klaver, J AU - Klaver J FAU - Vorpahl, J AU - Vorpahl J LA - eng GR - P30 CA14520/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Neurosurgery JT - Neurosurgery JID - 7802914 RN - 0 (Recombinant Proteins) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) SB - IM MH - Animals MH - Brain Neoplasms/metabolism/pathology/*physiopathology MH - Cell Movement/physiology MH - Glioma/metabolism/pathology/*physiopathology MH - Hepatocyte Growth Factor/biosynthesis/*physiology MH - Humans MH - Mice MH - Microglia/*physiology MH - Proto-Oncogene Proteins c-met/metabolism MH - Recombinant Proteins MH - Tumor Cells, Cultured EDAT- 1999/05/08 00:00 MHDA- 1999/05/08 00:01 CRDT- 1999/05/08 00:00 PHST- 1999/05/08 00:00 [pubmed] PHST- 1999/05/08 00:01 [medline] PHST- 1999/05/08 00:00 [entrez] AID - 10.1097/00006123-199905000-00075 [doi] PST - ppublish SO - Neurosurgery. 1999 May;44(5):1077-82; discussion 1082-3. doi: 10.1097/00006123-199905000-00075.