Invasive properties of serous human epithelial ovarian tumors are related to Ets-1, MMP-1 and MMP-9 expression.
The invasive potential of serous epithelial ovarian tumors is the main factor determining their biological behaviour. In contrast to invasive serous ovarian carcinomas serous borderline tumors generally present without stromal invasion and without or non-invading peritoneal implants. Little is known about the reasons underlying these differences. In the present study we found that two matrix-degrading metalloproteinases, collagenases 1 and 4 (MMPs 1 and 9), as well as the Ets-1 transcription factor are expressed at very low levels in serous benign cystadenomas, upregulated in the fibroblastic stroma, but not in the epithelium of borderline tumors and most strongly expressed in both stromal and epithelial tumor cells of serous invasive carcinomas. Since expression of Ets-1 and of MMPs 1 and 9 are topographically related, a transcriptional regulation of both proteases by Ets-1 is suggested. Upregulation of MMPs 1 and 9 within fibroblastic stromal cells of borderline tumors might be related to matrix remodelling and additional expression of both enzymes by the neoplastic cells of invasive carcinomas could then allow invasive propagation. The different expression patterns might supports the view, that no transition of serous borderline tumors into invasive carcinomas occurs.
Behrens
P
P
Institute of Pathology, University of Bonn, D-53105 Bonn, Germany.
Rothe
M
M
Florin
A
A
Wellmann
A
A
Wernert
N
N
D016475:3T3 Cells; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism* / Q000473:pathology; D003537:Cystadenoma / Q000378:metabolism / Q000473:pathology; D018293:Cystadenoma, Serous / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
C494041:ETS1 protein, human; C494042:Ets1 protein, mouse; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1