title: Microglia stimulate the invasiveness of glioma cells by increasing the activity of metalloprotease-2.
abstract: Gliomas represent the most frequent type of human brain tumor, and their strong invasiveness is a significant clinical problem. Microglia, the immunocompetent cells of the brain, contribute significantly to the tumor and are potential interaction partners of the glioma cells. We studied the impact of the presence of microglia on tumor cell invasion in cultured brain slices. To selectively deplete microglia, the slices were treated with clodronate-filled liposomes. When glioma cells were injected into slices devoid of endogenous microglia, the invasiveness of the tumors was significantly decreased as compared with controls. Inoculation of exogenous microglia together with glioma cells into cultured brain slices increased the infiltrative behavior of the tumor depending on the microglia/glioma cell ratio. Cell culture experiments revealed that soluble factors released from glioma cells strongly stimulate metalloprotease-2 activity in microglia. In the brain slices inoculated with glioma cells, increased activity of metalloprotease-2 was directly correlated with the abundance of microglia. Our data indicate that glioma cells stimulate microglial cells to increase breakdown of extracellular matrix and thereby promote tumor invasiveness.
authors.affiliation: Cellular Neuroscience Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany.
authors.forename: Darko S
authors.initials: DS
authors.lastname: Markovic
authors.forename: Rainer
authors.initials: R
authors.lastname: Glass
authors.forename: Michael
authors.initials: M
authors.lastname: Synowitz
authors.forename: Nico van
authors.initials: Nv
authors.lastname: Rooijen
authors.forename: Helmut
authors.initials: H
authors.lastname: Kettenmann
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D004002:Clodronic Acid / Q000008:administration & dosage; D005455:Fluorescent Antibody Technique; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008081:Liposomes; D008297:Male; D045726:Metalloproteases / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000201:enzymology*; D018613:Microscopy, Confocal; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009924:Organ Culture Techniques
chemical_list: D000963:Antimetabolites; D008081:Liposomes; D004002:Clodronic Acid; D045726:Metalloproteases