Increased matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 secretion but unaffected invasiveness of endometrial stromal cells in adenomyosis

Objective: To investigate cell invasiveness and the production of matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 in endometrial stromal cells (ESCs) of adenomyosis. Design: Prospective study. Setting: Tertiary university hospital. Patient(s): Twenty-one women with adenomyosis (study group) and 25 women without adenomyosis (control group). Intervention(s): Endometrial stromal cells were purified from eutopic endometrium and were cultured in vitro. Main Outcome Measure(s): Matrigel invasion assay and measurement of MMP-2, MMP-9, TIMP-1, and TIMP-2 concentrations. Result(s): Endometrial stromal cell invasiveness of adenomyosis was not different from that of the control group (0.95 vs. 1, using the latter as the bench mark) in ESCs cultured alone. After the ESCs were cultured with IL-6, anti-IL-6, or GM6001 for 24 hours, the indices of cell invasion were not different between the two groups. MMP-2 (median 7.3 vs. 3.5 ng/mL) and TIMP-1 (median 12.1 vs. 3.9 ng/mL), but not MMP-9 and TIMP-2, secreted by ESCs in women with adenomyosis were much higher than those in women without adenomyosis. Conclusion(s): The formation of adenomyosis does not result from altered invasiveness of ESCs. The concomitant elevation of MMP-2 and TIMP-1 may partially justify why invasiveness was not increased, but other enzymes should also be considered.