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

Abstract

Background: Matrix metalloproteinases (MMPs) play a crucial role in cancer progression and metastasis, however their role in pediatric Acute lymphoblastic leukemia (ALL) is still unrevealed. Methods: The diagnostic, prognostic and predictive value of tissue inhibitor of metalloproteinase (TIMP-1), MMP-2, MMP-9 and CD34+CD38− cancer stem cells (CSCs) were assessed in bone marrow (BM) samples of 76 ALL children using Flow Cytometry analysis. Results: There was a significant increase in TIMP-1 [1.52 (0.41-10) versus 0.91(0.6-1.12); respectively, p < 0.001], and CSCs CD34 + CD38 − [1 (0.03-18.6) versus 0.3 (0.01-1.1), p < 0.001] expression in ALL patients compared to controls. While there were no significant differences regarding MMP-2 and MMP-9 expression between the two groups. The sensitivity, specificity, area under curve (AUC) of MMP-2 were (80.3%, 53.3% and 0.568, p = 0.404), and of MMP-9 were (53.9%, 40% and 0.660, p = 0.053). While that of TIMP-1 were (78.9%, 100% and 0.892, p < 0.001), and that of CD34 + CD38 − CSCs were (78.9%, 73.3% and 0.855, p < 0.001). Increased TIMP-1 expression associated with the high-risk disease (p < 0.001). CD34 + CD38 − CSCs and MMP-2 overexpression associated with MRD at day-15, increased BM blast cell count at diagnosis and at day-15 (p < 0.05). TIMP-1 overexpression is associated with shorter DFS and OS rates (p = 0.009 and p = 0.048). Multivariate logistic regression analysis showed that both TIMP-1 [OR: 4.224, p = 0.046], and CD34 + CD38 − CSCs [OR: 6.873, p = 0.005] could be potential independent diagnostic factors for pediatric ALL. Conclusion: TIMP-1 and CD34 + CD38 − CSCs could be possible useful diagnostic markers for pediatric ALL. Also, TIMP-1 is a promising prognostic marker for poor outcome of the patients.

The anti-adhesion effect of nisin as a robust lantibiotic on the colorectal cancer cells

“…[ 32 ] Furthermore, high expression of MMP-2 and MMP-9 is related to metastasis to lymph nodes. [ 33 ] MMP-9 are able to secrete the ECM factors such as TGF-β, VEGF, and FGF-2 causing to proliferate and migrant endothelial cells and finally angiogenesis. [ 34 ]…”

Effect of CB2 Stimulation on Gene Expression in Pediatric B-Acute Lymphoblastic Leukemia: New Possible Targets

“…In 2016, Xiao-yu Gao described how TMSB4X regulates MMP-2 expression levels via the Wnt/β-catenin/Lef-1 signaling pathway influencing cell migration. MMPs have a key role in hematopoietic stem cell mobilization, as well as in cancer-allowing progression and invasion [ 52 ]. Even though their role in ALL is not yet very clear, they could represent a good target for both prognosis and therapy, since they play a key role in tumor angiogenesis and metastasis [ 53 ].…”

Naringin: antitumor potential in silico and in vitro on bladder cancer cells

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