Association of Type IV Collagenase Activation Potential With Metastatic Progression in Human Ovarian Carcinoma Cell Lines

Lee, S H; Bae, S N; Kim, J D; Park, J S; Kim, S J

Abstract

Our purpose in this study was to detect the secretory pattern and the degree of enzymatic activity of MMP-2 and to evaluate the invasive activty in vitro in each cancer cell line, using four kinds of human ovarian cancer cell lines (CAOV-4, SW626, NIH: OVCAR-3, and SK-OV-3) as well as MCF-7MMP-2 cell line which secretes recombinant 72-kDa MMP-2 as an inactive form. The results were as follows; 1. An inactive form of MMP-2 was secreted by all ovarian cancer cell lines, but the activated form of MMP-2 was also secreted by NIH: OVCAR-3, SK-OV-3, and SW626. 2. In the Boyden chamber chemoinvasion assay, the invasive activity was shown in SK-OV-3, NIH: OVCAR-3, SW626, and CAOV-4 cell lines in order. This finding corresponds with the secretory pattern of 62 kDa MMP-2, activated form. 3. In the outgrowth morphology on Matrigel, the dendritic processes of NIH: OVCAR-3 and SK-OV-3 cell lines were seen to emerge more actively than those of SW626 and CAOV-4 cell lines. NIH: OVCAR-3 and SK-OV-3 cell lines also had a clustered formation. 4. An inactive form of MMP-2 secreted by CAOV-4 was activated by the treatment with Concanavalin A, MMP-2 activator. 5. The productions and secretions of MMP-2 in SK-OV-3, NIH: OVCAR-3, and SW626 cell lines were inhibited by the treatment with cycloheximide, MMP-2 inhibitor. From the above results, we showed that the invasion and metastasis of human ovarian cancr cell lines have directly relations with MMP-2. It was identified that the secretory patterns of activated MMP-2 were closely associated with the invasiul activity of human ovarian cancer cell lines in vitro and that the MMP-2 secreted by human ovarian cancer cell lines might been activated or inhibited by enzyme regulators. In the future, we wish this study applied to the metastatic prevention and treatment of human ovarian cancer by using enzyme regulators.