Cytokine-regulated expression of collagenase-2 (MMP-8) is involved in the progression of ovarian cancer.
Matrix metalloproteinases (MMPs) have been implicated in ovarian cancer progression. Among them, MMP-8 that degrades type I collagen may play a crucial role. The aim of our study was to determine MMP-8 expression and regulation in ovarian cancer and its association with other MMPs and tissue inhibitors of metalloproteinases (TIMPs). Tissue microarrays (TMAs) containing tissue cylinders from 302 patients were used for immunohistochemical studies. In addition, MMP-8 expression in vitro was analysed by a specific immunoassay and PCR-analysis. MMP-7 (81%), MMP-8 (95%), MT3-MMP (100%), TIMP-2 (100%), and TIMP-3 (96%) were expressed in all the OVCAs, but the staining intensities varied. MMP-3 (6%), MMP-9 (57%) and TIMP-1 (43%) expressions were more rarely detected. Only MMP-8 expression levels correlated with tumour grade (P<0.01), tumour stage (P<0.01), and a poor prognosis (P<0.05). MMP-8 protein and gene expression in vitro was found to be significantly upregulated by interleukin-1beta (IL-1beta, P<0.01). The data indicate that MMP-8 overexpression in OVCAs is regulated by IL-1beta and that pro-inflammatory cytokines may promote the invasive potential of ovarian cancer.
Institute of Pathology, University of Innsbruck, Muellerstrasse 44, 6020 Innsbruck, Austria. sylvia.stadlmann@uibk.ac.at
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S
Stadlmann
J
J
Pollheimer
P L
PL
Moser
A
A
Raggi
A
A
Amberger
R
R
Margreiter
F A
FA
Offner
G
G
Mikuz
S
S
Dirnhofer
H
H
Moch
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D016207:Cytokines / Q000494:pharmacology*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000201:enzymology*; D011379:Prognosis; D016019:Survival Analysis
D016207:Cytokines; D020784:Matrix Metalloproteinase 8