title: Matrix-degrading proteases ADAMTS4 and ADAMTS5 (disintegrins and metalloproteinases with thrombospondin motifs 4 and 5) are expressed in human glioblastomas.
abstract: Brain tumors, in particular glioblastomas, have a high morbidity and mortality, mainly due to their invasive nature. A prerequisite for this invasiveness is cell migration based on increased expression of proteases digesting the extracellular matrix. Brevican, an important extracellular proteoglycan that is upregulated in glioblastomas, can be degraded by certain proteases. We demonstrate that in human glioblastomas secretory proteases like ADAMTS4 and ADAMTS5 (aggrecanases 1 and 2; ADAMTS = a disintegrin and metalloproteinase with thrombospondin motifs) are expressed on the mRNA and protein levels in considerable amounts. Real-time RT-PCR shows a higher levels of ADAMTS4 and 5 expressions in glioblastomas in situ, compared to cultured human glioblastoma cells. The upregulation of these proteases in vivo by cytokines may explain this difference. In vitro, transforming growth factor-beta induces ADAMTS4, but less ADAMTS5, and interleukin-1beta ADAMTS5, but not ADAMTS4. As demonstrated by immunohistochemistry and confocal microscopy in situ, ADAMTS5 expression is confined to proliferating glioblastoma cells of surgical tumor sections and with lower intensity to astroglial cells in normal brain sections, as opposed to brevican. In vitro, glioblastoma-derived ADAMTS5 degrades recombinant human brevican to several smaller fragments. Our results show that ADAMTS4 and 5 are upregulated on proliferating glioblastoma cells and these proteases may contribute to their invasive potential.
authors: Department of Neurosurgery, University of Kiel, Kiel, Germany.
authors: Janka
authors: J
authors: Held-Feindt
authors: Elke Bernedo
authors: EB
authors: Paredes
authors: Ulrike
authors: U
authors: Blömer
authors: Constanze
authors: C
authors: Seidenbecher
authors: Andreas M
authors: AM
authors: Stark
authors: H Maximilian
authors: HM
authors: Mehdorn
authors: Rolf
authors: R
authors: Mentlein
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis*; D000071121:ADAMTS4 Protein; D000071116:ADAMTS5 Protein; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D009361:Neoplasm Invasiveness; D011348:Procollagen N-Endopeptidase / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human