title: Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma.
abstract: MMPs (matrix metalloproteinases), ADAMs (a disintegrin and metalloproteinase) and TIMPs (tissue inhibitors of metalloproteinases) are implicated in invasion and angiogenesis: both are tissue remodeling processes involving regulated proteolysis of the extracellular matrix, growth factors and their receptors. The expression of these three groups and their correlations with clinical behaviour has been reported in gliomas but a similar comprehensive study in meningiomas is lacking. In this study, we aimed to evaluate the patterns of expression of 23 MMPs, 4 TIMPs, 8 ADAMs, selective growth factors and their receptors in 17 benign meningiomas using a quantitative real-time polymerase chain reaction (qPCR). Results indicated very high gene expression of 13 proteases, inhibitors and growth factors studied: MMP2 and MMP14, TIMP-1, -2 and -3, ADAM9, 10, 12, 15 and 17, EGF-R, EMMPRIN and VEGF-A, in almost every meningioma. Expression pattern analysis showed several positive correlations between MMPs, ADAMs, TIMPs and growth factors. Furthermore, our findings suggest that expression of MMP14, ADAM9, 10, 12, 15 and 17, TIMP-2, EGF-R and EMMPRIN reflects histological subtype of meningioma such that fibroblastic subtype had the highest mRNA expression, transitional subtype was intermediate and meningothelial type had the lowest expression. In conclusion, this is the first comprehensive study characterizing gene expression of 8 ADAMs in meningiomas. These neoplasms, although by histological definition benign, have invasive potential. Taken together, the selected elevated gene expression pattern may serve to identify targets for therapeutic intervention or indicators of biological progression and recurrence.
authors: Department of Neurosurgery, King's College Hospital, London SE5 9RS, UK.
authors: Harcharan K
authors: HK
authors: Rooprai
authors: Department of Neurosurgery, St. George's Hospital, London SW17 0QT, UK.
authors: Andrew J
authors: AJ
authors: Martin
authors: Department of Clinical Neuropathology, King's College Hospital, London SE5 9RS, UK.
authors: Andrew
authors: A
authors: King
authors: School of Science and Technology, Middlesex University, London NW4 4BT, UK.
authors: Usha D
authors: UD
authors: Appadu
authors: School of Science and Technology, Middlesex University, London NW4 4BT, UK.
authors: Huw
authors: H
authors: Jones
authors: Department of Neurosurgery, King's College Hospital, London SE5 9RS, UK.
authors: Richard P
authors: RP
authors: Selway
authors: Department of Neurosurgery, King's College Hospital, London SE5 9RS, UK.
authors: Richard W
authors: RW
authors: Gullan
authors: School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK.
authors: Geoffrey J
authors: GJ
authors: Pilkington
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D051926:Basigin / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D008579:Meningioma / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051926:Basigin; C512478:EGFR protein, human; D066246:ErbB Receptors; D051722:ADAM Proteins; D020782:Matrix Metalloproteinases