Abstract
Matrix metalloproteinase (MMP)-9 and neutrophil gelatinase-associated lipocalin (NGAL) have gained attention as cancer biomarkers. The inactive zymogen form of MMP-9 (pro-MMP-9) also exists as a disulphide-linked heterodimer bound to NGAL in humans. Leukaemias represent a heterogeneous group of neoplasms, which vary in their clinical behavior and pathophysiology. In this review, we summarize the current literature on the expression profiles of pro-MMP-9 and NGAL as prognostic factors in leukaemias. We also report the expression of the pro-MMP-9/NGAL complex in these diseases. We discuss the roles of (pro)-MMP-9 (active and latent forms) and NGAL in tumour development, and evaluate the mechanisms by which pro-MMP-9/NGAL may influence the actions of (pro)-MMP-9 and NGAL in cancer. Emerging knowledge about the coexpression and the biology of (pro)-MMP-9, NGAL and their complex in cancer including leukaemia may improve treatment outcomes.
Highlights
Of the matrix metalloproteinases (MMPs) thought to be involved in cancer, attention has focused on Matrix metalloproteinase (MMP)-9 because of its deregulated expression in cancer and its association with tumours’ invasive potential [1,2]
Like pro-MMP-9, Neutrophil gelatinase-associated lipocalin (NGAL) is shown to interact as ligand with integral membrane proteins and this may induce a receptor-mediated effect on signalling pathways involved in biological events (Figure 2)
It is legitimate to suggest that the pro-MMP-9/NGAL complex could interfere with the binding of NGAL and/or pro-MMP-9 to their respective receptors, modulating signalling events induced by pro-MMP-9 and/or NGAL (Figure 2)
Summary
Of the matrix metalloproteinases (MMPs) thought to be involved in cancer, attention has focused on MMP-9 because of its deregulated expression in cancer and its association with tumours’ invasive potential [1,2]. Normal immature (CD34+) bone marrow progenitor cells express NGAL [20] but not (pro)MMP-9 [21]. Bone marrow and blood mononuclear cells from CML patients express pro-MMP-9 and NGAL proteins [12,43,44,45]. If CML patients achieve complete molecular remission after imatinib therapy, NGAL serum levels fall and are significantly lower than the disease-state value [47,48]. Bone marrow pro-MMP-9 levels are significantly lower in AML patients than in normal controls; the levels recover to normal values following complete remission and decline again at relapse [35]. These evidences further support the multiple roles of MMP-9 observed in cancer and summarized below
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
