Invasiveness corresponds to differentiation rather than to proteinase secretion in endometrial cancer cell lines

Local invasiveness is an important prognostic factor in endometrial carcino ma. To study the role of two groups of secreted proteinases (serine protein ases and matrix metalloproteinases) in this process, we examined three endo metrial cancer cell lines (Ishikawa HEC 1A, AN3CA) for their invasiveness i n vitro. Additionally, we considered the secretion of urokinase type plasmi nogen activator (uPA), plasminogen activator inhibitor 1 and 2 (PAI-1 and P AI-2), as well as matrix metalloproteinases (MMP) 1, 2, 3, and 9, and their inhibitors TIMP-1 and TIMP-2. Compared to the highly invasive fibrosarcoma cell line HT1080, Ishikawa displayed low and AN3CA moderate invasiveness, while HEC1A cells were almost as invasive as HT 1080 cells. Ishikawa cells secreted the highest amounts of proteinases. Cytokine and steroid treatment s upregulated MMP-1 in all cell lines while the effects were heterogeneous regarding other proteinases and inhibitors. No effect of these treatments o n invasiveness could be detected. Both basal secretion and regulation of th e proteinases tested in this set of experiments seem to be markers of diffe rentiation rather than of invasiveness.