ESTABLISHMENT OF LONG-TERM IN-VITRO CULTURES OF HUMAN OVARIAN CYSTADENOMAS AND LMP TUMORS AND EXAMINATION OF THEIR SPECTRUM OF EXPRESSION OF MATRIX-DEGRADING PROTEINASES

Objectives. To obtain long-term cultures of ovarian cystadenomas and o varian tumors of low malignant potential (LMP) displaying gene express ion patterns similar to those found in vivo and test the hypothesis th at such cultures would express different levels of matrix-degrading pr oteinases than cultured ovarian carcinomas. Methods. Transfection with an adenoviral expression vector for simian virus 40 (SV40) large T an tigen was used to establish long-term cultures of the above tumors, Le vels of expression of various genes were evaluated using molecular bio logical and immunohistochemical approaches, Zymography and reverse zym ography were used to examine the activity of various metalloproteinase s and plasminogen activators (PA), Two-sided P values for differences in plasminogen activator expression between different cell types were evaluated by Fisher's exact test. Results. Long-term cultures derived from cystadenomas and LMP tumors were obtained which formed colonies o n semisolid supports, but were not tumorigenic in nude mice, The cultu red cells expressed keratin, estrogen receptor, gonadotropin receptors , BRCA1, and originated from monoclonal populations, There was no appa rent association between the malignant phenotype and the expression of either matrix metalloproteinases or tissue inhibitors of metalloprote inases. However, a correlation was seen between this phenotype and exp ression of urokinase (uPA) and tissue type (tPA) plasminogen activator s (P = 0.08 and 0.02 respectively). Conclusions. The above cell strain s provide a useful model for investigating various aspects of the biol ogy of benign ovarian tumors, including their response to steroid and gonadotropin hormones, and the role of specific proteinases in the acq uisition of invasive and metastatic abilities. (C) 1997 Academic Press .