The expression of
matrix metalloproteinases (
MMPs) is often associated with invasiveness or grade of tumours. Increased blood levels of
MMP proteins, including MMP-1, MMP-2, MMP-3 and MMP-9 have been detected in various types of
cancers. With the exception of one study,
MMPs in serum and plasma have been determined using ELISA. In the present study we measured the activity of the
MMPs found in human plasma samples using
gelatin enzymography and fluorimetric degradation assays. We used plasma samples from healthy control subjects and
cancer patients enrolled in a dose-finding study for the
MMP inhibitor,
BAY 12-9566, to assess the activity of
MMPs found in plasma and screen for efficacy of the
MMP inhibitor.
BAY 12-9566 has inhibitory activity toward MMP-2, MMP-3 and MMP-9. Patients with advanced solid tumours were enrolled in our study and plasma was collected on day 1 before dosing and at steady-state of the
drug on day 15. Our results show that
BAY 12-9566 was effective in lowering the plasma gelatinolytic activity in the group of 29 patients when considering the data obtained from a fluorimetric
gelatinase assay. The data obtained from
gelatin enzymography, however, did not reach significance. The fluorimetric degradation assay could be a useful tool to screen plasma from
cancer patients in other clinical trials assessing
MMP inhibitors.