title: Expression of matrix metalloproteinases MMP-1, MMP-11 and MMP-19 is correlated with the WHO-grading of human malignant gliomas.
abstract: Glioblastomas (GBM) are the most prevalent type of malignant primary brain tumor in adults. They may manifest de novo or develop from low-grade astrocytomas (LGA) or anaplastic astrocytomas. They are characterized by an aggressive local growth pattern and a marked degree of invasiveness, resulting in poor prognosis. Tumor progression is facilitated by an increased activity of proteolytic enzymes such as matrix metalloproteinases (MMPs). Elevated levels of several MMPs were found in glioblastomas compared to LGA and normal brain (NB). However, data for some MMPs, like MMP-1, are controversially discussed and other MMPs like MMP-11 and MMP-19 have as yet not been analysed in detail. We examined the expression of MMP-1, MMP-9, MMP-11 and MMP-19 in NB, LGA and GBM by semiquantitative RT-PCR, Western blotting and immunohistochemistry and found an enhanced expression of these MMPs in GBM compared to LGA or NB in signal strength and in the percentage of tumors displaying MMP expression. The transition from LGA to GBM was characterized by a shift of pro-MMP-11 to expression of the active enzyme. Therefore, MMP-1, MMP-11 and MMP-19 might be of importance for the development of high-grade astrocytic tumors and may be promising targets for therapy.
authors.affiliation: University of Würzburg, Department of Neurosurgery, Tumorbiology Laboratory, Josef-Schneider-Strasse 11, D-97080 Würzburg, Germany.
authors.forename: Jelena
authors.initials: J
authors.lastname: Stojic
authors.forename: Carsten
authors.initials: C
authors.lastname: Hagemann
authors.forename: Stefanie
authors.initials: S
authors.lastname: Haas
authors.forename: Christian
authors.initials: C
authors.lastname: Herbold
authors.forename: Siglinde
authors.initials: S
authors.lastname: Kühnel
authors.forename: Stefanie
authors.initials: S
authors.lastname: Gerngras
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Roggendorf
authors.forename: Klaus
authors.initials: K
authors.lastname: Roosen
authors.forename: Giles Hamilton
authors.initials: GH
authors.lastname: Vince
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D001932:Brain Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000201:enzymology*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005910:Glioma / Q000145:classification / Q000175:diagnosis* / Q000201:enzymology*; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D053507:Matrix Metalloproteinase 11 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D014944:World Health Organization
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D053507:Matrix Metalloproteinase 11; D053505:Matrix Metalloproteinases, Secreted; C108362:matrix metalloproteinase 19; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1