Journal
EUROPEAN JOURNAL OF CANCER
Volume 39, Issue 17, Pages 2499-2505Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2003.08.011
Keywords
matrix metalloproteinases; collagenase-2; MMP-8; ovarian cancer; pro-inflammatory cytokines; tissue inhibitor of matrix metalloproteinases; TIMP; tissue microarray; TMA
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Matrix metalloprotemases (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 metalloprotemases (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-1 beta (IL-10, P<0.01). The data indicate that MMP-8 overexpression in OVCAs is regulated by IL-10 and that proinflammatory cytokines may promote the invasive potential of ovarian cancer. (C) 2003 Elsevier Ltd. All rights reserved.
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