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.

ABSTRACT

OBJECTIVES: To obtain long-term cultures of ovarian cystadenomas and ovarian tumors of low malignant potential (LMP) displaying gene expression patterns similar to those found in vivo and test the hypothesis that such cultures would express different levels of matrix-degrading proteinases than cultured ovarian carcinomas. METHODS: Transfection with an adenoviral expression vector for simian virus 40 (SV40) large T antigen was used to establish long-term cultures of the above tumors. Levels of expression of various genes were evaluated using molecular biological and immunohistochemical approaches. Zymography and reverse zymography were used to examine the activity of various metalloproteinases 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 on semisolid supports, but were not tumorigenic in nude mice. The cultured cells expressed keratin, estrogen receptor, gonadotropin receptors, BRCA1, and originated from monoclonal populations. There was no apparent association between the malignant phenotype and the expression of either matrix metalloproteinases or tissue inhibitors of metalloproteinases. However, a correlation was seen between this phenotype and expression of urokinase (uPA) and tissue type (tPA) plasminogen activators (P = 0.08 and 0.02 respectively). CONCLUSIONS: The above cell strains provide a useful model for investigating various aspects of the biology of benign ovarian tumors, including their response to steroid and gonadotropin hormones, and the role of specific proteinases in the acquisition of invasive and metastatic abilities.