Potential of fluorescent metalloproteinase substrates for cancer detection

ObjectivesMMP-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 methodsSubstrates with varying specificities for MMP-9 and MMP-2 and several ADAMs were screened. Flsub21 and Flsub13, substrates for ADAM12 and ADAM8 respectively, were studied.ResultsFlsub21 and Flsub13 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 Flsub21 and Flsub13 were positive, 65% when Flsub21 alone was positive, 55% when Flsub13 alone was positive and 20% when both substrates were negative.ConclusionsThese data suggest the potential utility of FRET substrates to non-invasively identify invasive and/or metastatic breast cancer.

► We analyzed proteolysis of FRET substrates in urine of breast cancer patients and controls.
► Flsub21 and Flsub13 cleavages are detected at significantly higher frequencies in urine of breast patients.
► FRET substrates may be used to non-invasively identify invasive and/or metastatic breast cancer.