Matrix Metalloproteinase-19 Is Expressed in Myeloid Cells in an Adhesion-Dependent Manner and Associates with the Cell Surface

The role of membrane-type (MT) 2-matrix metalloproteinase (MMP) in the cellular activation of MMP-2 and the tissue inhibitor of matrix metalloproteinase (TIMP) requirements for this process have not been clearly established. To address these issues a TIMP-2-free cell line derived from aTimp2−/− mouse was transfected for stable cell surface expression of hMT2-MMP. Untransfected cells did not activate endogenous or exogenous TIMP-2-free MMP-2 unless both TIMP-2 and concanavalin A (ConA) were added. Transfected cells expressing hMT2-MMP efficiently activated both endogenous and exogenous MMP-2 (within 4 h) via the 68-kDa intermediate in the absence of TIMP-2 and ConA. In contrast, activation of MMP-2 byTimp2−/− cells expressing recombinant hMT1-MMP occurred more slowly (12 h) and required the addition of 0.3–27 nmTIMP-2. Addition of TIMP-2 or TIMP-4 did not enhance MMP-2 activation by MT2-MMP at any concentration tested; furthermore, activation was inhibited by both TIMPs at concentrations >9 nm, consistent with the similar association rate constants (kon) calculated for the binding of TIMP-4 and TIMP-2 to MT2-MMP (3.56 × 105m−1s−1and 6.52 × 105m−1s−1, respectively). MT2-MMP-mediated activation involved cell surface association of the MMP-2 in a hemopexin carboxyl-terminal domain (C domain)-dependent manner: Exogenous MMP-2 hemopexin C domain blocked activation, and cells expressing hMT2-MMP did not bind or activate a truncated form of MMP-2 lacking the hemopexin C domain. These studies demonstrate the existence of an alternative TIMP-2-independent pathway for MMP-2 activation involving MT2-MMP, which may be important in mediating MMP-2 activation in specific tissues or pathologies where MT2-MMP is expressed.

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Faculty Opinions recommendation of Proteolysis of cell-surface tissue transglutaminase by matrix metalloproteinase-2 contributes to the adhesive defect and matrix abnormalities in thrombospondin-2-null fibroblasts and mice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1028943.342441 ◽

2005 ◽

Author(s):

Helen Gruber

Keyword(s):

Cell Surface ◽

Matrix Metalloproteinase ◽

Tissue Transglutaminase ◽

Matrix Metalloproteinase 2

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Antimetastatic Effects of Sesamin on Human Head and Neck Squamous Cell Carcinoma through Regulation of Matrix Metalloproteinase-2

Molecules ◽

10.3390/molecules25092248 ◽

2020 ◽

Vol 25 (9) ◽

pp. 2248 ◽

Cited By ~ 1

Author(s):

Jian-Ming Chen ◽

Pei-Yin Chen ◽

Chia-Chieh Lin ◽

Ming-Chang Hsieh ◽

Jen-Tsun Lin

Keyword(s):

Oral Cancer ◽

Matrix Metalloproteinase ◽

Head And Neck ◽

Mapk Pathway ◽

Human Head ◽

Mapk Signaling ◽

Matrix Metalloproteinase 2 ◽

Migration And Invasion ◽

Dependent Manner

Background: Sesamin is a lignin present in sesame oil from the bark of Zanthoxylum spp. Sesamin reportedly has anticarcinogenic potential and exerts anti-inflammatory effects on several tumors. Hypothesis/Purpose: However, the effect of sesamin on metastatic progression in human head and neck squamous carcinoma (HNSCC) remains unknown in vitro and in vivo; hence, we investigated the effect of sesamin on HNSCC cells in vitro. Methods and Results: Sesamin-treated human oral cancer cell lines FaDu, HSC-3, and Ca9-22 were subjected to a wound-healing assay. Furthermore, Western blotting was performed to assess the effect of sesamin on the expression levels of matrix metalloproteinase (MMP)-2 and proteins of the MAPK signaling pathway, including p-ERK1/2, P-p38, and p-JNK1/2. In addition, we investigated the association between MMP-2 expression and the MAPK pathway in sesamin-treated oral cancer cells. Sesamin inhibited cell migration and invasion in FaDu, Ca9-22, and HSC-3 cells and suppressed MMP-2 at noncytotoxic concentrations (0 to 40 μM). Furthermore, sesamin significantly reduced p38 MAPK and JNK phosphorylation in a dose-dependent manner in FaDu and HSC-3 cells. Conclusions: These results indicate that sesamin suppresses the migration and invasion of HNSCC cells by regulating MMP-2 and is thus a potential antimetastatic agent for treating HNSCC.

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New Insights on NETosis Induced by Entamoeba histolytica: Dependence on ROS from Amoebas and Extracellular MPO Activity

Antioxidants ◽

10.3390/antiox10060974 ◽

2021 ◽

Vol 10 (6) ◽

pp. 974

Author(s):

César Díaz-Godínez ◽

Joshue Fabián Jorge-Rosas ◽

Mario Néquiz ◽

Santiago Martínez-Calvillo ◽

Juan P. Laclette ◽

...

Keyword(s):

Cell Surface ◽

Nadph Oxidase ◽

Entamoeba Histolytica ◽

Pathogen Detection ◽

Dependent Manner ◽

Antimicrobial Proteins ◽

Nadph Oxidase Activity ◽

Mitochondrial Ros ◽

Pre Treatment ◽

Dose Dependent

NETosis is a neutrophil process involving sequential steps from pathogen detection to the release of DNA harboring antimicrobial proteins, including the central generation of NADPH oxidase dependent or independent ROS. Previously, we reported that NETosis triggered by Entamoeba histolytica trophozoites is independent of NADPH oxidase activity in neutrophils, but dependent on the viability of the parasites and no ROS source was identified. Here, we explored the possibility that E. histolytica trophozoites serve as the ROS source for NETosis. NET quantitation was performed using SYTOX® Green assay in the presence of selective inhibitors and scavengers. We observed that respiratory burst in neutrophils was inhibited by trophozoites in a dose dependent manner. Mitochondrial ROS was not also necessary, as the mitochondrial scavenger mitoTEMPO did not affect the process. Surprisingly, ROS-deficient amoebas obtained by pre-treatment with pyrocatechol were less likely to induce NETs. Additionally, we detected the presence of MPO on the cell surface of trophozoites after the interaction with neutrophils and found that luminol and isoluminol, intracellular and extracellular scavengers for MPO derived ROS reduced the amount of NET triggered by amoebas. These data suggest that ROS generated by trophozoites and processed by the extracellular MPO during the contact with neutrophils are required for E. histolytica induced NETosis.

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Mechanical Control of Cell Migration by the Metastasis Suppressor Tetraspanin CD82/KAI1

Cells ◽

10.3390/cells10061545 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1545

Author(s):

Laura Ordas ◽

Luca Costa ◽

Anthony Lozano ◽

Christopher Chevillard ◽

Alexia Calovoulos ◽

...

Keyword(s):

Cell Migration ◽

Cell Surface ◽

Focal Adhesion ◽

Nuclear Translocation ◽

Single Cells ◽

Integral Membrane Protein ◽

Metastasis Suppressor ◽

Dependent Manner ◽

Strong Inhibitor ◽

Caveolin 1

The plasma membrane is a key actor of cell migration. For instance, its tension controls persistent cell migration and cell surface caveolae integrity. Then, caveolae constituents such as caveolin-1 can initiate a mechanotransduction loop that involves actin- and focal adhesion-dependent control of the mechanosensor YAP to finely tune cell migration. Tetraspanin CD82 (also named KAI-1) is an integral membrane protein and a metastasis suppressor. Its expression is lost in many cancers including breast cancer. It is a strong inhibitor of cell migration by a little-known mechanism. We demonstrated here that CD82 controls persistent 2D migration of EGF-induced single cells, stress fibers and focal adhesion sizes and dynamics. Mechanistically, we found that CD82 regulates membrane tension, cell surface caveolae abundance and YAP nuclear translocation in a caveolin-1-dependent manner. Altogether, our data show that CD82 controls 2D cell migration using membrane-driven mechanics involving caveolin and the YAP pathway.

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Abstract P204: Epithelial Sodium Channel Stimulation by Glucose

Hypertension ◽

10.1161/hyp.68.suppl_1.p204 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Parijat S Joy ◽

Peter M. Snyder

Keyword(s):

Diabetes Mellitus ◽

Cell Surface ◽

Collecting Duct ◽

Short Circuit ◽

Primary Cultures ◽

Endocytic Pathway ◽

Sodium Absorption ◽

Dependent Manner ◽

Elevated Glucose ◽

Underlying Mechanisms

There is a link between diabetes mellitus and hypertension, but the underlying mechanisms are poorly understood. The epithelial Na + channel ENaC plays an important role in blood pressure control; ENaC mutations cause Liddle’s syndrome, an inherited form of hypertension. Previous work suggests that ENaC abundance is increased in diabetes mellitus, but the underlying mechanisms are unclear. Here we tested the effect of glucose on ENaC regulation. In Ussing chamber experiments using mouse kidney collecting duct cells (mCCD) and primary cultures of human lung epithelia, elevated glucose increased ENaC-mediated short-circuit current by 2-3 times in a dose-dependent manner from 100mg/dl to 400mg/dl of glucose. This was caused by an increase in ENaC abundance at the cell surface. We hypothesized that hyperglycemia might enhance ENaC cell surface abundance by altering activity of Nedd4-2, an E3 ubiquitin-protein ligase that binds to PY motifs within ENaC. Consistent with this hypothesis, we found that mutation of the PY motifs abolished ENaC stimulation by elevated glucose. Moreover, using a biotinylation assay, we found that elevated glucose (300 mg/dl) slowed ENaC endocytosis and reduced its degradation in the endocytic pathway. These changes in trafficking are explained by our finding that glucose reduced ENaC binding to Nedd4-2, and hence, reduced ENaC ubiquitination. O-GlcNAcylation plays a role in insulin signaling and glucose toxicity due to increased O-GlcNAcylation of target proteins. To test a role for O-GlcNAcylation in ENaC stimulation by glucose, we used 6-Diazo-5-oxo-l-norleucine (DON) to inhibit O-GlcNAcylation. DON abolished ENaC stimulation by elevated glucose. Using anti-O-GlcNAc antibody, we found that Nedd4-2 is a substrate for O-GlcNAcylation, and this modification was increased by elevated glucose. DON also reversed the reduction in binding of Nedd4-2 to ENaC at high glucose levels. Together, our data suggest a model in which hyperglycemia stimulates ENaC through O-GlcNAcylation of Nedd4-2, increasing ENaC abundance at cell surface thus increasing epithelial sodium absorption.

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Cell surface interactions in conjugation: Tetrahymena ciliary membrane vesicles

Molecular and Cellular Biology ◽

10.1128/mcb.4.4.681-687.1984 ◽

1984 ◽

Vol 4 (4) ◽

pp. 681-687

Author(s):

B Love ◽

M B Rotheim

Keyword(s):

Cell Surface ◽

Mating Type ◽

Mammalian Cells ◽

Membrane Vesicles ◽

Surface Interactions ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Ciliary Membrane ◽

Adhesion Sites ◽

Cell Surface Interactions

Tetrahymena ciliary membrane vesicles are shown to interact with preconjugant cells in a mating type-specific way. When cells are treated with vesicles of a different mating type before mixing for conjugation, cell pairing is enhanced, and the normal prepairing period is partially eliminated. This enhancement is mating type specific since it is not observed after pretreatment of cells with vesicles of their own mating type. In contrast, when vesicles are added at the time of mixing of two starved cultures, cell pairing is delayed in a concentration-dependent manner. By varying the conditions, we demonstrated enhancement or inhibition, or both. These results are interpreted in terms of two independent interactions of cells with vesicles. We suggest that first, vesicles substitute for another cell in cell-cell prepairing interaction and second, vesicles compete for adhesion sites produced during the prepairing period. Finally, the data presented are summarized within a speculative framework that calls attention to potential analogies with hormone-receptor signaling in mammalian cells.

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All-Trans Retinoic Acid Enhances Matrix Metalloproteinase 2 Expression and Secretion in Human Myeloid Leukemia THP-1 Cells

BioMed Research International ◽

10.1155/2018/5971080 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Hien Thi Vu ◽

Thi Xoan Hoang ◽

Jae Young Kim

Keyword(s):

Retinoic Acid ◽

Matrix Metalloproteinase ◽

Calcium Ion ◽

Myeloid Leukemia ◽

Leukemia Cell Line ◽

Matrix Metalloproteinase 2 ◽

Migration And Invasion ◽

Dependent Manner ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid

All-trans retinoic acid (ATRA) is an effective drug for the induction therapy of acute promyelocytic leukemia. However, the treatment is associated with adverse events such as retinoic acid syndrome (RAS) in some patients, whose histologic characteristics included organ infiltration by leukemic cells. Matrix metalloproteinase 2 (MMP-2) is often upregulated in tumor cells and plays a role in tumor cell migration and invasion by degrading the extracellular matrix. In this study, we examined the possible modulatory effects of ATRA on MMP-2 expression and secretion in human myeloid leukemia cell line THP-1. The cells were treated with various concentrations of ATRA, and MMP-2 expression and secretion were examined. MMP-2 expression and secretion started to increase with ATRA concentration as low as 0.1 nM and gradually increased thereafter. Agonists of retinoic acid receptor (RAR) or retinoid X receptor (RXR) alone could enhance MMP-2 secretion, and RAR or RXR antagonists alone could reverse ATRA-induced MMP-2 secretion. ATRA increased intracellular calcium ion levels, and a calcium-channel blocker inhibited ATRA-induced MMP-2 secretion. Dexamethasone suppressed ATRA-induced MMP-2 secretion. Our results suggest that ATRA enhances MMP-2 expression and secretion in human myeloid leukemia THP-1 cells in a calcium ion dependent manner through RAR/RXR signaling pathways, and this enhanced expression and secretion may be associated with the possible mechanisms of RAS.

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Cutaneous T Cell Lymphoma Expresses Immunosuppressive CD80 (B7-1) Cell Surface Protein in a STAT5-Dependent Manner

The Journal of Immunology ◽

10.4049/jimmunol.1302951 ◽

2014 ◽

Vol 192 (6) ◽

pp. 2913-2919 ◽

Cited By ~ 17

Author(s):

Qian Zhang ◽

Hong Yi Wang ◽

Fang Wei ◽

Xiaobin Liu ◽

Jennifer C. Paterson ◽

...

Keyword(s):

T Cell ◽

Cell Surface ◽

Cell Lymphoma ◽

Surface Protein ◽

T Cell Lymphoma ◽

Dependent Manner ◽

Cutaneous T Cell Lymphoma ◽

Cell Surface Protein

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Adhesion of uric acid crystals to the surface of renal epithelial cells

AJP Renal Physiology ◽

10.1152/ajprenal.2000.278.6.f989 ◽

2000 ◽

Vol 278 (6) ◽

pp. F989-F998 ◽

Cited By ~ 44

Author(s):

Rima M. Koka ◽

Erick Huang ◽

John C. Lieske

Keyword(s):

Uric Acid ◽

Epithelial Cells ◽

Cell Surface ◽

Hydrophobic Interactions ◽

Calcium Phosphates ◽

Apical Cell ◽

Apical Surface ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Renal Tubular Cells

Adhesion of microcrystals that nucleate in tubular fluid to the apical surface of renal tubular cells could be a critical step in the formation of kidney stones, 12% of which contain uric acid (UA) either alone or admixed with calcium oxalates or calcium phosphates. UA crystals bind rapidly to monolayer cultures of monkey kidney epithelial cells (BSC-1 line), used to model the surface of the nephron, in a concentration-dependent manner. The urinary glycoproteins osteopontin, nephrocalcin, and Tamm-Horsfall glycoprotein had no effect on binding of UA crystals to the cell surface, whereas other polyanions including specific glycosaminoglycans blocked UA crystal adhesion. Specific polycations also inhibited adhesion of UA crystals and appeared to exert their inhibitory effect by coating cells. However, removal of anionic cell surface molecules with neuraminidase, heparitinase I, or chondroitinase ABC each increased UA crystal binding, and sialic acid-binding lectins had no effect. These observations suggest that hydrogen bonding and hydrophobic interactions play a major role in adhesion of electrostatically neutral UA crystals to renal cells, unlike the interaction of calcium-containing crystals with negatively charged molecules on the apical cell surface via ionic forces. After adhesion to the plasma membrane, subsequent cellular events could contribute to UA crystal retention in the kidney and the development of UA or mixed calcium and UA calculi.

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