Program in Vascular Biology and Department of Surgery, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
Clin Biochem. 2011 Dec;44(17-18):1434-9. doi: 10.1016/j.clinbiochem.2011.09.016. Epub 2011 Oct 6.
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.
Substrates 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.
Flsub21 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.
These data suggest the potential utility of FRET substrates to non-invasively identify invasive and/or metastatic breast cancer.
MMP-2、MMP-9、它们的复合物和 ADAM12 可在乳腺癌患者的尿液中检测到,并可预测疾病状态。我们评估了基于 FRET 的底物在区分乳腺癌患者和对照中的应用。
筛选了针对 MMP-9 和 MMP-2 以及几种 ADAMs 的特异性不同的底物。分别研究了 ADAM12 和 ADAM8 的底物 Flsub21 和 Flsub13。
与对照组相比,侵袭性和转移性乳腺癌患者的尿液中 Flsub21 和 Flsub13 的裂解活性明显更高。当 Flsub21 和 Flsub13 均为阳性时,我们的模型预测概率为 90%,当 Flsub21 单独为阳性时预测概率为 65%,当 Flsub13 单独为阳性时预测概率为 55%,而当两种底物均为阴性时预测概率为 20%。
这些数据表明 FRET 底物具有非侵入性识别侵袭性和/或转移性乳腺癌的潜在用途。