Potential of fluorescent metalloproteinase substrates for cancer detection

Objectives: MMP-2, MMP-9, their complexes and ADAM12 are detected in the urine of breast cancer patients and predict disease status. We assessed the use of FRET-based substrates in an assay to distinguish breast cancer patients from controls. Design and methods: Substrates with varying specificities for MMP-9 and MMP-2 and several ADAMs were screened. FIsub21 and FIsub13, substrates for ADAM12 and ADAM8 respectively, were studied. Results: FIsub21 and FIsub13 cleavage activities were detected in the urine of patients with invasive and metastatic breast cancers at significantly higher frequencies compared to controls. Our model predicted probabilities of 90% when both FIsub21 and FIsub13 were positive, 65% when FIsub21 alone was positive, 55% when Flsub13 alone was positive and 20% when both substrates were negative. Conclusions: These data suggest the potential utility of FRET substrates to non-invasively identify invasive and/or metastatic breast cancer. (C) 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.