Levels of active forms of MMP-1, MMP-2, and MMP-9 as independent prognostic factors for differentiating the stage and type of lung cancer (SCLC and NSCLC)

Abstract

Despite years of research on the development and treatment of cancer, its diagnosis still remains at an unsatisfactory level. Constant efforts are needed to identify new and more specific tumor markers for improving early diagnosis. Metalloproteinases (MMPs) are interesting candidates, worthy of consideration, given their potential impact on tumor progression through changes in both their levels and activity. In this study, we propose a biosensor featuring a single-step design and voltammetric detection to monitor both the levels and the activities of three MMPs, MMP-1, MMP-2, and MMP-9, particularly relevant in the context of lung cancer, during a single measurement. To simplify the biosensor construction as much as possible, receptors in the form of thiolated tripeptides, labeled with redox probes (highly specific for each MMP action), were synthesized. Each receptor was labeled with a different redox probe to enable the simultaneous detection of the three selected MMPs. The developed biosensor was characterized by its high stability, high sensitivity, and low detection limits of 10.5, 13.7, and 8.4 fg·mL−1 for MMP-1, MMP-2, and MMP-9, respectively. To prove that MMPs are excellent biomarkers not only for the early diagnosis of lung cancer but also for distinguishing the type of cancer and determining the stage of the disease, the studies were conducted on tissue extracts obtained from mice implanted with H446 and A549 cell lines, representing small cell and non–small cell lung cancer, respectively.