Journal: Experimental Hematology & Oncology

Article Title: MMP14 from BM-MSCs facilitates progression and Ara-C resistance in acute myeloid leukemia via the JAK/STAT pathway

doi: 10.1186/s40164-025-00635-6

Figure Lengend Snippet: Combined transcriptomic and proteomic analyses identified MMP14 as a key molecule in AMLMSC supporting leukemia cell growth. A , B . Analysis of apoptosis in primary leukemia cells after 48 h of co-culture with five cases each of AML-MSC and HD-MSC, using the Annexin V APC Apoptosis Detection Kit ( n = 5). Alone, leukemia cells cultured alone; Co, leukemia cells cocultured with MSCs. C , D . Flow BrdU assay for assessing the proliferation of primary leukemia cells after 48 h of co-culture with 5 AMLMSC and 5 HDMSC cases( n = 5). E . Volcano plots displaying the expression of differentially expressed genes between five AML-MSC and five HD-MSC samples, with purple representing upregulation and blue representing downregulation( n = 5). F . Enrichment analysis of differentially expressed genes. G . Proteomic analysis of supernatants from 4 AML-MSC and 4 HD-MSC samples, including a heat map of differentially expressed proteins( n = 4). H . Intersection analysis of differentially expressed genes identified in transcriptomic and proteomic analyses. I . Kaplan-Meier survival analysis of OHSU-AML dataset revealed that high expression of MMP14 is associated with poorer overall survival. J . PCR detection of MMP14 expression in AMLMSC ( n = 12) compared to HDMSC ( n = 6). K . Co-immunohistochemical staining of MMP14 (red) and CD271 (green) in AML and healthy control bone marrow samples. Scale bar = 20 μm ( n = 5)

Article Snippet: The MMP14 inhibitor NSC 405020 was purchased from MCE (HY-15827, China).

Techniques: Co-Culture Assay, Cell Culture, BrdU Staining, Expressing, Immunohistochemical staining, Staining, Control

Journal: Experimental Hematology & Oncology

Article Title: MMP14 from BM-MSCs facilitates progression and Ara-C resistance in acute myeloid leukemia via the JAK/STAT pathway

doi: 10.1186/s40164-025-00635-6

Figure Lengend Snippet: Effects of MMP14 on MSC proliferation and cytokine secretion. A , B . Knockdown efficiency of MMP14 in MSCs verified by Western blot and RT-qPCR. C , D . Representative plots of CFU-F in the MMP14 knockdown and control groups. Quantification of CFU-F colonies in MSCs. E , F . BrdU assay showing cell proliferation rates in the MMP14 knockdown and control groups. G , H . Cell cycle analysis of the MMP14 knockdown and control groups. I - K . After co-culturing Kasumi-1 and Molm-13 cells with MSCs from the knockdown and control groups for 48 h, flow sorting was performed on the MSCs followed by PCR analysis of TGF-β1, CXCL12, CXCL10, OPN, and COX-2 gene expression levels

Article Snippet: The MMP14 inhibitor NSC 405020 was purchased from MCE (HY-15827, China).

Techniques: Knockdown, Western Blot, Quantitative RT-PCR, Control, BrdU Staining, Cell Cycle Assay, Gene Expression

Journal: Experimental Hematology & Oncology

Article Title: MMP14 from BM-MSCs facilitates progression and Ara-C resistance in acute myeloid leukemia via the JAK/STAT pathway

doi: 10.1186/s40164-025-00635-6

Figure Lengend Snippet: Knockdown of MSC-derived MMP14 significantly inhibits AML progression in vitro. A - C . Flow cytometry analysis of apoptosis rates in Kasumi-1 and Molm-13 cells co-cultured with the knockdown and control groups for 48 h. D - F . Flow cytometry PI analysis of cell cycle changes in Kasumi-1 and Molm-13 cells co-cultured with the knockdown and control groups for 48 h. G - I . Flow cytometry BrdU analysis of cell proliferation rates in Kasumi-1 and Molm-13 cells co-cultured with the knockdown and control groups for 48 h

Article Snippet: The MMP14 inhibitor NSC 405020 was purchased from MCE (HY-15827, China).

Techniques: Knockdown, Derivative Assay, In Vitro, Flow Cytometry, Cell Culture, Control

Journal: Experimental Hematology & Oncology

Article Title: MMP14 from BM-MSCs facilitates progression and Ara-C resistance in acute myeloid leukemia via the JAK/STAT pathway

doi: 10.1186/s40164-025-00635-6

Figure Lengend Snippet: Effect of MMP14 deletion in MSCs on disease progression and leukemic stem cells in MLL-AF9 leukemic mice. ( A ) The experimental layout involved transplanting MLL-AF9 cells via the tail vein and MSCs from MMP14 knockdown and control groups via intra-femoral injection into mice. AML progression was monitored by flow cytometric analysis. ( B ) Survival rates of mice in MMP14 knockdown and control groups after cell transplantation ( n = 7). ( C ) Live imaging was performed on days 14, 21, and 28 post-transplant to monitor disease progression and burden( n = 5). D , E . Flow cytometry plots of BM LSCs and statistical analysis of the proportion of LSC in whole BM ( n = 4). F . Statistical analysis of the proportion of leukemia cells in mice of both groups ( n = 4). G . Bone marrow cell count statistics in both groups of mice ( n = 4). H , I . Representative flow cytometry plots of LSC apoptosis and statistical analysis of the apoptosis rate of LSCs ( n = 4). J , K . Representative flow cytometry plots of the LSC cell cycle and statistical analysis of the percentage of apoptosis in LSCs ( n = 4)

Article Snippet: The MMP14 inhibitor NSC 405020 was purchased from MCE (HY-15827, China).

Techniques: Knockdown, Control, Injection, Transplantation Assay, Imaging, Flow Cytometry, Cell Counting

Journal: Experimental Hematology & Oncology

Article Title: MMP14 from BM-MSCs facilitates progression and Ara-C resistance in acute myeloid leukemia via the JAK/STAT pathway

doi: 10.1186/s40164-025-00635-6

Figure Lengend Snippet: MMP14 exerts its functions by activating the JAK-STAT pathway in AML cells through the secretion of PGE2. ( A ) Transcriptome analysis of Kasumi-1 cells co-cultured with MSCs from the MMP14 knockdown and control groups after 48 h. Volcano plots are shown. ( B ) Heat map of differentially expressed genes. ( C ) Enrichment analysis of differentially expressed genes. ( D ) GSEA analysis showing that MMP14 knockdown in MSCs is associated with inhibition of the JAK-STAT pathway. ( E ) Western blot analysis of STAT3, P-STAT3, STAT5, and P-STAT5 protein levels in Kasumi-1 and Molm-13 cells co-cultured with MSCs from the MMP14 knockdown and control groups. ( F ) ELISA assay of PGE2 levels in the supernatant of MSCs from the MMP14 knockdown and control groups. ( G ) ELISA assay of PGE2 levels in the serum of mice from the MMP14 knockdown group and the control group. H-J. Proliferation of Kasumi-1 and Molm-13 cells in the presence or absence of PGE2 (1 μm) in the co-culture system of the knockdown and control groups

Article Snippet: The MMP14 inhibitor NSC 405020 was purchased from MCE (HY-15827, China).

Techniques: Cell Culture, Knockdown, Control, Inhibition, Western Blot, Enzyme-linked Immunosorbent Assay, Co-Culture Assay

Journal: Experimental Hematology & Oncology

Article Title: MMP14 from BM-MSCs facilitates progression and Ara-C resistance in acute myeloid leukemia via the JAK/STAT pathway

doi: 10.1186/s40164-025-00635-6

Figure Lengend Snippet: MMP14 confers chemoresistance to Ara-C. A . Overview of the experimental design, dividing mice into four groups based on the presence or absence of the inhibitor (NSC-405020) and cytarabine. B . Survival statistics of mice ( n = 7). C - E . Representative FACS analysis and statistical proportions of leukemia cells in the four groups of mice ( n = 4). F . Representative images of Wright-Giemsa staining of bone marrow cells and hematoxylin-eosin staining of spleens. G . Representative images of mouse spleens. H - J . Immunohistochemical staining of P-STAT3 and P-STAT5 in mouse bone marrow and quantification of the staining. Scale bar, 50 μm

Article Snippet: The MMP14 inhibitor NSC 405020 was purchased from MCE (HY-15827, China).

Techniques: Staining, Immunohistochemical staining

Journal: Experimental Hematology & Oncology

Article Title: MMP14 from BM-MSCs facilitates progression and Ara-C resistance in acute myeloid leukemia via the JAK/STAT pathway

doi: 10.1186/s40164-025-00635-6

Figure Lengend Snippet: Inhibition of MMP14 suppressed AML patient blasts. A - C . Flow cytometry analysis of apoptosis rates in primary leukemia cells co-cultured with the knockdown and control groups for 48 h. Alone, leukemia cells cultured alone; Co, leukemia cells cocultured with MSCs. D , E . Viable cells were counted using trypan blue staining and assessed with a hemocytometer after 48 h of co-culturing. F . Schematic of the PDX model construction process. Primary human leukemia cells were isolated from high-leukemia AML patients using leukapheresis and PBMC separation. These cells were then injected into NSG mice via the tail vein. Four weeks later, one mouse per week was randomly sacrificed, and the proportion of leukemia cells in the BM was analyzed by flow cytometry. Drug treatment commenced when the leukemia cell proportion reached ≥ 20%. Following successful PDX model construction, mice were randomly allocated to four treatment groups: DMSO-treated control (Ctrl), MMP14 inhibitor (inhibitor), cytarabine (Ara-C), and a combination of MMP14 inhibitor and cytarabine (inhibitor + Ara-C). G . Survival statistics for the mice were compiled ( n = 6). H-J. Flow cytometric representative plots and statistical analysis detailing the proportion and absolute numbers of human CD45 + cells in the four mouse groups ( n = 5)

Article Snippet: The MMP14 inhibitor NSC 405020 was purchased from MCE (HY-15827, China).

Techniques: Inhibition, Flow Cytometry, Cell Culture, Knockdown, Control, Staining, Isolation, Injection

Journal: Experimental Hematology & Oncology

Article Title: MMP14 from BM-MSCs facilitates progression and Ara-C resistance in acute myeloid leukemia via the JAK/STAT pathway

doi: 10.1186/s40164-025-00635-6

Figure Lengend Snippet: Mechanism of action of MSC-derived MMP14 in promoting AML progression. The model illustrates how MSC-derived MMP14 promotes AML cell growth and chemotherapy resistance through the secretion of PGE2, activating the JAK-STAT pathway, leading to AML progression. Additionally, MSC-derived MMP14 enhances MSC proliferation and self-renewal, while also inducing cytokine alterations

Article Snippet: The MMP14 inhibitor NSC 405020 was purchased from MCE (HY-15827, China).

Techniques: Derivative Assay

Journal: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

Article Title: Cherubism mice also deficient in c-Fos exhibit inflammatory bone destruction executed by macrophages that express MMP14 despite the absence of TRAP+ osteoclasts

doi: 10.1002/jbmr.3295

Figure Lengend Snippet: (A) Immunohistochemical staining of inflammatory lesions at the distal tibia from c-Fos-deficient Sh3bp2KI/KI mouse with anti-F4/80 antibody. 12 weeks old. Bar = 100 μm. (B) qPCR analysis of macrophage marker gene expression in the ankle joints. (C) μCT images of the distal tibia at 12 weeks old. (D) Quantitative measurement of eroded bone surface area at the distal tibia. (E) qPCR analysis of Tnf expression in the ankle joints. (F) qPCR analysis of Mmp2 and Mmp14 expression in the ankle joints. (G) Western blotting analysis of MMP2 and MMP14 with cell lysates from the ankle joints. (H) μCT images of the distal tibia from Sh3bp2KI/KI mice treated with or without an MMP14 inhibitor NSC405020 (50 mg/kg/day) from 4 to 10 weeks old. (I) Quantitative measurement of eroded bone surface area at the distal tibia of Sh3bp2KI/KI mice treated with or without NSC405020 from 4 to 10 weeks old. (J) Comparison of Mmp14 expression levels in fetal liver-derived M-CSF-dependent macrophages by qPCR. n = 3. (K) Measurement of collagenolytic activity of fetal liver-derived M-CSF-dependent macrophages. n = 6. (L) Measurement of collagenolytic activity of fetal liver-derived M-CSF-dependent macrophages in the presence or absence of NSC405020. n = 6. (M) Measurement of mineral resorption capacity of fetal liver-derived M-CSF-dependent macrophages. n = 6. Macrophages were cultured for 7 days on the plates coated with europium-labeled type I collagen fibers (K, L) or on the plates coated with fluoresceinamine-labeled calcium phosphate (M). Average expression levels in wild-type mice are set as 1 (B, E, F). Average expression level in wild-type mice at day 2 is set as 1 (J). Data are presented as mean ± SD. *p < 0.05 with two-tailed t-test (D, E, F, I) or ANOVA with Tukey-Kramer post-hoc test (B, J, K, L, M). NS = not significant.

Article Snippet: For inhibition of MMP14 activity in vivo , c-Fos −/− Sh3bp2 KI/KI mice were administrated with NSC405020 ( 39 ) (50 mg/kg/day, AdooQ Bioscience) or DX-2400 ( 40 ) (40 and 200 mg/kg, every other day, Kadmon Corp.) subcutaneously from 4 to 10 weeks old.

Techniques: Immunohistochemical staining, Staining, Marker, Gene Expression, Expressing, Western Blot, Comparison, Derivative Assay, Activity Assay, Cell Culture, Labeling, Two Tailed Test

Journal: Biosensors

Article Title: Detecting the PEX Like Domain of Matrix Metalloproteinase-14 (MMP-14) with Therapeutic Conjugated CNTs

doi: 10.3390/bios12100884

Figure Lengend Snippet: ( A ) Schematic representation of NSC405020 molecule grafted onto CNTs surface followed by ( B ) SEM images for pristine, acylated, and inhibitor loaded CNTs (low and high magnification).

Article Snippet: 3,4-Dichloro-N-(pentan-2-yl) benzamide, (MMP-14 Inhibitor- NSC405020 (AmBeed, Arlington Heights, IL, USA)) was grafted onto acylated CNTs.

Techniques:

Journal: Biosensors

Article Title: Detecting the PEX Like Domain of Matrix Metalloproteinase-14 (MMP-14) with Therapeutic Conjugated CNTs

doi: 10.3390/bios12100884

Figure Lengend Snippet: ( A ) Nyquist plots of inhibitor loaded CNTs before and after interaction with different concentrations of MPP-14 for 10 minutes in PBS (pH 7.40) containing 10 mmol.mL −1 of K 3 [Fe (CN) 6 ] − and 10 mmol.mL −1 of NaCl. ( B ) Linear fit of EIS response for different concentrations of MMP-14, presenting LOD of 7.5 ng⋅mL −1 . Significant difference between measurements was obtained at p -value < 0.05 (n = 2). Protein concentration varying from 10 ng.mL −1 to 100 ng.mL −1 , applied potential of +0.20 V, from 50 kHz to 500 Hz, amplitude 50 mV.

Article Snippet: 3,4-Dichloro-N-(pentan-2-yl) benzamide, (MMP-14 Inhibitor- NSC405020 (AmBeed, Arlington Heights, IL, USA)) was grafted onto acylated CNTs.

Techniques: Protein Concentration

Journal: Biosensors

Article Title: Detecting the PEX Like Domain of Matrix Metalloproteinase-14 (MMP-14) with Therapeutic Conjugated CNTs

doi: 10.3390/bios12100884

Figure Lengend Snippet: ( A ) The inhibitor/protein interaction between small molecule NSC 405020 and the binding pocket of MMP-14 and ( B ) Schematic of the MMP-14 detection through the binding mechanism of protein and inhibitory small molecule as the recognition element.

Article Snippet: 3,4-Dichloro-N-(pentan-2-yl) benzamide, (MMP-14 Inhibitor- NSC405020 (AmBeed, Arlington Heights, IL, USA)) was grafted onto acylated CNTs.

Techniques: Binding Assay

Journal: Biosensors

Article Title: Detecting the PEX Like Domain of Matrix Metalloproteinase-14 (MMP-14) with Therapeutic Conjugated CNTs

doi: 10.3390/bios12100884

Figure Lengend Snippet: EIS response for the inhibitor loaded CNT after individual interaction with 50 ng⋅mL −1 of MMP-1 and MMP-14 in PBS (pH 7.40) containing 10 mmol⋅mL −1 of K 4 [Fe (CN) 6 ] − 10 mmol⋅mL −1 of K 3 [Fe (CN) 6 ] − and 10 mmol⋅mL −1 of NaCl. The inhibitor loaded CNT showed specificity to MMP-14 (applied potential of +0.20 V, from 50 kHz to 500 Hz, amplitude 50 mV).

Article Snippet: 3,4-Dichloro-N-(pentan-2-yl) benzamide, (MMP-14 Inhibitor- NSC405020 (AmBeed, Arlington Heights, IL, USA)) was grafted onto acylated CNTs.

Techniques:

Journal: Oxidative Medicine and Cellular Longevity

Article Title: Matrix Metalloproteinase 14 Mediates APP Proteolysis and Lysosomal Alterations Induced by Oxidative Stress in Human Neuronal Cells

doi: 10.1155/2020/5917187

Figure Lengend Snippet: Modulation of MMP14 levels and the enzyme's subcellular location by oxidative stress. (a, b) SK-N-MC cells were treated with X-XOD in the presence or absence of NSC405020 for 24 h. (c, d) MMP14 deficient cells (clone 3) and control cells (clone 8), generated as described in Methods, were treated with X-XOD for 24 h. (a, c) Western blotting was performed using anti-MMP14 and anti- α -tubulin antibodies. The image shows a representative experiment, and the bar graph below the relative ratio versus control cells (mean + SEM) of the densitometric value of MMP14 normalized against α -tubulin. ∗ p < 0.05 and ∗∗ p < 0.01 (Student's t -test, n = 7 independent experiments for inhibited and n = 4 independent experiments for deficient cells). (b, d) After incubation for 24 h, cells were examined by confocal microscopy. The representative panel shows immunofluorescence images for anti-MMP14 antibody. Original magnification: 63x. Scale bar: 10 μ m. No staining was observed when the primary antibody was omitted.

Article Snippet: NSC405020 (APExBIO), a cell-permeable pentanylbenzamide compound that acts as an allosteric, reversible, and selective inhibitor of the collagenolytic activity of MMP14 [ ], was added to the cells at a concentration of 100 μ M at the same time as X-XOD.

Techniques: Control, Generated, Western Blot, Incubation, Confocal Microscopy, Immunofluorescence, Staining

Journal: Oxidative Medicine and Cellular Longevity

Article Title: Matrix Metalloproteinase 14 Mediates APP Proteolysis and Lysosomal Alterations Induced by Oxidative Stress in Human Neuronal Cells

doi: 10.1155/2020/5917187

Figure Lengend Snippet: Effect of MMP14 inhibition or silencing on the accumulation of the APP 85 kDa fragment induced by OS. (a, b) SK-N-MC cells were treated with X-XOD in the presence or absence of NSC405020 for 24 h. (c, d) MMP14 deficient cells (clone 3) and control (clone 8) were treated with X-XOD for 24 h. (a, c) Western blotting was performed using 22C11 and anti- α -tubulin antibodies. The image shows a representative experiment, and the bar graph below the relative ratio versus control cells (mean + SEM) of the densitometric value of APP (white bars) and the APP85 fragment (black bars) normalized against α -tubulin. ∗ p < 0.05 and ∗∗ p < 0.01 (Student's t -test, n = 4 independent experiments). (b, d) After incubation for 24 h, cells were examined by confocal microscopy. The representative panel shows immunofluorescence images for 22C11 antibody. Original magnification: 63x. Scale bar: 10 μ m. No staining was observed when the primary antibodies were omitted.

Article Snippet: NSC405020 (APExBIO), a cell-permeable pentanylbenzamide compound that acts as an allosteric, reversible, and selective inhibitor of the collagenolytic activity of MMP14 [ ], was added to the cells at a concentration of 100 μ M at the same time as X-XOD.

Techniques: Inhibition, Control, Western Blot, Incubation, Confocal Microscopy, Immunofluorescence, Staining

Journal: Oxidative Medicine and Cellular Longevity

Article Title: Matrix Metalloproteinase 14 Mediates APP Proteolysis and Lysosomal Alterations Induced by Oxidative Stress in Human Neuronal Cells

doi: 10.1155/2020/5917187

Figure Lengend Snippet: Effect of MMP14 inhibition or gene silencing on the increase in lysosome load induced by OS. (a–c, e–g) SK-N-MC cells were treated with X-XOD in the presence or absence of NSC405020 for 24 h. (d, h) MMP14 deficient cells (clone 3) and control (clone 8) were treated with X-XOD. (a, b) Western blotting was performed using (a) anti-CD63, (b) anti-LAMP2, and anti- α -tubulin antibodies. The image shows a representative experiment, and the bar graph below the relative ratio versus control cells (mean + SEM) of the densitometric value normalized against α -tubulin. ∗ p < 0.05 and ∗∗ p < 0.01 (Student's t -test, n = 4 independent experiments). (c, d) After incubation for 24 h, the lysosome load was analyzed by fluorimetric measurement using LysoTracker. The graph shows the mean (±SEM) fluorescence expressed as a percentage of the control value. ∗ p < 0.05, ∗∗ p < 0.01, and ∗∗∗ p < 0.01 ( t -test, n = 4 independent experiments). (e–g) After incubation for 24 h, cells were examined by confocal microscopy. The representative panel shows immunofluorescence images for (e) anti-CD63, (f) anti-LAMP2, and (g) LysoTracker. Original magnification: 63x. Scale bar: 10 μ m. No staining was observed when the primary antibodies were omitted. (h) After incubation for 24 h, control or MMP14 deficient cells were examined by Western blotting using anti-CD63 and anti- α -tubulin antibodies.

Article Snippet: NSC405020 (APExBIO), a cell-permeable pentanylbenzamide compound that acts as an allosteric, reversible, and selective inhibitor of the collagenolytic activity of MMP14 [ ], was added to the cells at a concentration of 100 μ M at the same time as X-XOD.

Techniques: Inhibition, Control, Western Blot, Incubation, Fluorescence, Confocal Microscopy, Immunofluorescence, Staining

Journal: Oxidative Medicine and Cellular Longevity

Article Title: Matrix Metalloproteinase 14 Mediates APP Proteolysis and Lysosomal Alterations Induced by Oxidative Stress in Human Neuronal Cells

doi: 10.1155/2020/5917187

Figure Lengend Snippet: Validation of results in human iPSC-derived neural cells. (a, c, e, f) NPCs and (b, d) neurons were treated with X-XOD in the presence or absence of NSC405020 for 24 h. Western blotting was performed using (a, b) anti-MMP14, (c, d) 22C11, (e) anti-CD63, and anti- α -tubulin antibodies. The image shows a representative experiment, and the bar graph below the relative ratio versus control cells (mean + SEM) of the densitometric value (APP (white bars) and APP85 fragment (black bars)) normalized against α -tubulin. ∗ p < 0.05 and ∗∗ p < 0.01 (Student's t -test, NPCs n = 3 independent experiments and neurons n = 1; CD63 n = 2 independent experiments). (f) After incubation for 24 h, NPCs were examined by confocal microscopy. The representative panel shows immunofluorescence images for anti-CD63 antibody. Original magnification: 63x. Scale bar: 10 μ m.

Article Snippet: NSC405020 (APExBIO), a cell-permeable pentanylbenzamide compound that acts as an allosteric, reversible, and selective inhibitor of the collagenolytic activity of MMP14 [ ], was added to the cells at a concentration of 100 μ M at the same time as X-XOD.

Techniques: Biomarker Discovery, Derivative Assay, Western Blot, Control, Incubation, Confocal Microscopy, Immunofluorescence