Selected Matrix Metalloproteinases (MMP-2, MMP-7) and Their Inhibitor (TIMP-2) in Adult and Pediatric Cancer

Abstract

The tumor microenvironment (TME) consists of numerous biologically relevant elements. One of the most important components of the TME is the extracellular matrix (ECM). The compounds of the ECM create a network that provides structural and biochemical support to surrounding cells. The most important substances involved in the regulation of the ECM degradation process are matrix metalloproteinases (MMPs) and their endogenous inhibitors (tissue inhibitors of metalloproteinases, TIMPs). The disruption of the physiological balance between MMP activation and deactivation could lead to progression of various diseases such as cardiovascular disease, cancer, fibrosis arthritis, chronic tissue ulcers, pathologies of the nervous system (such as stroke and Alzheimer’s disease), periodontitis, and atheroma. MMP-TIMP imbalance results in matrix proteolysis associated with various pathological processes such as tumor invasion. The present review discusses the involvement of two MMPs, MMP-2 and MMP-7, in cancer pathogenesis. These two MMPs have been proven in several studies, conducted mostly on adults, to make an important contribution to cancer development and progression. In the current review, several studies that indicate the importance of MMP-TIMP balance determination for the pediatric population are also highlighted. The authors of this review believe that carrying out biochemical and clinical studies focused on metalloproteinases and their inhibitors in tumors in children will be of great relevance for future patient diagnosis, determination of a prognosis, and monitoring of therapy.

Role of Matrix Metalloproteinase MMP-2, MMP-9 and Tissue Inhibitor of Metalloproteinase (TIMP-1) in Clinical Progression of Pediatric Acute Lymphoblastic Leukemia

“…In concordance with our results regarding the MMP-9/TIMP-1 ratio, Scrideli et al [32], observed no signi cant association between the MMP-9/TIMP-1 ratio and survival rate or the clinico-pathological features of the patients.…”

“…On the other hand, Verma et al [31], proposed that leukemia cells in B-ALL, may remodel the BMM via the secretion of certain factors inducing the expression of MMP-9, and therefore, increasing tumor's invasiveness. Indeed, the certain role of MMPs and TIMPs in ALL is not yet clear, especially in the pediatric population who have an extremely a heterogeneous nature of cancer [32]. In an attempt to investigate their diagnostic roles for childhood ALL, the present results demonstrated that TIMP-1 achieved the highest speci city (100%), and AUC (0.892) with a sensitivity of 78.9% for diagnosing pediatric patients with ALL.…”

“…Similarly, CD34+CD38-CSCs correlated signi cantly with MMP-2, MMP-9, and TIMP-1 expression. This observation indicates that there is a disruption occurred in the physiological balance between MMPs and TIMPs, which lead to matrix proteolysis that associated with different pathological diseases including cancer progression and metastasis [32]. Also, the nding of the signi cant correlation between CD34+CD38-CSCs and the assessed markers could be explained by the data observed by Verma et al [31], who reported that B-ALL cells can cause remodelling in the BMM by stimulating MMP-9 expression in the MSCs through the release of TNFα.…”

Identification of potential micro-messenger RNAs (miRNA–mRNA) interaction network of osteosarcoma

“…MMP2 is a member of the MMP gene family, which has the ability to cleave ECM components and participate in signal transduction. MMPs and their endogenous inhibitors (tissue inhibitors of metalloproteinases, TIMPs) are the most important substances in the regulation of the ECM degradation process [39] biomarkers associated with the invasion and metastasis of OS, which provides a new perspective on early diagnosis and finding novel therapeutic targets for OS patients. However, the present study has several limitations.…”

Role of matrix metalloproteinase MMP-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP-1) in the clinical progression of pediatric acute lymphoblastic leukemia

“…On the other hand, Verma et al [32], proposed that leukemia cells in B-ALL, may remodel the BMM via the secretion of certain factors inducing the expression of MMP-9, and therefore, increasing tumor's invasiveness. Indeed, the certain role of MMPs and TIMPs in ALL is not yet clear, especially in the pediatric population who have an extremely a heterogeneous nature of cancer [33]. In an attempt to investigate their diagnostic roles for childhood ALL, the present results demonstrated that TIMP-1 achieved the highest specificity (100%), and AUC (0.892) with a sensitivity of 78.9% for diagnosing pediatric patients with ALL.…”