SEARCH · PubMed Health

Results for “Matrix”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources

PubMed1995

Matrix metalloproteinase 7 (matrilysin) from human rectal carcinoma cells. Activation of the precursor, interaction with other matrix metalloproteinases and enzymic properties.

Matrix metalloproteinase 7 (MMP-7) has been purified as an inactive zymogen of M(r) 28,000 (proMMP-7) from the culture medium of CaR-1 human rectal carcinoma cells. The NH2-terminal sequence of proMMP-7 is Lys-Pro-Lys-Pro-Gln-Glu, which is identical to that of matrilysin. The zymogen is activated by 4-aminophenylmercuric acetate (APMA), yielding an intermediate form of M(r) 21,000 and an active species of M(r) 19,000 which shows the new NH2-terminal sequence of Tyr78-Ser-Leu-Phe-Pro-Asn-Ser. Although trypsin fully activates the zymogen, the activation rate by plasmin or leukocyte elastase is confined to approximately 50%. ProMMP-7 can be activated by MMP-3 (stromelysin 1) to its full activity in a single-step mechanism and generates the same NH2 terminus obtained by APMA activation, whereas MMP-1 (tissue collagenase), MMP-2 (gelatinase A), and MMP-9 (gelatinase B) do not have such an effect. On the other hand, proMMP-1 is activated by MMP-7 to an activity similar to that obtained by APMA and the activation by MMP-7 is enhanced up to approximately 6.5 fold in the presence of APMA. This enhanced activity is donated by specific cleavage at the Gln80-Phe81 bond of proMMP-1. MMP-7 can also activate proMMP-9 up to approximately 50% of the full activity with a new NH2 terminus of Leu16-Arg-Thr-(Asn)-Leu. Incubation of proMMP-2 or proMMP-3 with MMP-7 results in no activation of these proMMPs. MMP-7 degrades type IV collagen, laminin-1, fibronectin, proteoglycan, type I gelatin, and insoluble elastin. These results suggest that in vivo MMP-7 may play a role in degradation of extracellular matrix macromolecules in concert with MMP-1, -3, and -9 under pathological conditions.

Collagenases↗

PubMed1997

Plasminogen activator and matrix metalloproteinase production and extracellular matrix degradation by rat prostate cancer cells in vitro: correlation with metastatic behavior in vivo.

BACKGROUND: The plasminogen activation (PA) and metalloproteinase (MMP) system are involved in tumor cell migration and invasion. METHODS: The proteolytic activity of cell lines originating from the rat Dunning R-3327 prostate tumor was analyzed by measuring in vitro extracellular matrix degradation, enzyme activity, and mRNA levels of enzymes, inhibitors, and receptors, and compared with their known metastatic behavior in vivo. RESULTS: Only the highly metastatic sublines AT-3, MATLu, and MATLyLu showed a high extracellular matrix degradation mediated by urokinase-type plasminogen activator (u-PA). Relatively high levels of u-PA were present in the aggressive cell lines. u-PA receptor mRNA was produced in all cells, and all but AT-1 produced LDL-receptor-related-protein (LRP) mRNA. t-PA mRNA was only found in HIF and MATLu. In gelatin, zymography lysis was observed at 72 kD and 74-76 kD in MATLu and MATLyLu cells, respectively. MMP-2 mRNA was present in all cell lines except AT-1 and AT-2, and MMP-3 mRNA was present in AT-2, AT-3, and MATLu. CONCLUSIONS: These in vitro experiments show that in different rat prostate cancer sublines, proteolytic activity and u-PA-mediated extracellular matrix degradation correlate with their known metastatic behavior in vivo.

Analysis of Variance↗

PubMed1993

The sign of Leser-Trélat: a cutaneous sign of internal malignancy: weakened subepithelial matrix from the effect of neoplasms on the extracellular matrix of the host.

The sudden onset of many seborrheic keratoses (SK) associated with an internal malignancy (most commonly adenocarcinoma) is called the sign of Leser-Trélat. It is associated with acanthosis nigricans (AN) in 20% of the cases. There are marked changes in the extracellular matrix (ECM) around tumors. Various fractions and depolymerized glycosaminoglycans enter circulation. They can incorporate in the general extracellular matrix. Mechanical factors present in AN produce extrusions of this poor quality ECM in the form of papillae and folds. The poor quality of subepithelial extracellular matrix produces the marked epithelial changes of acanthosis nigricans which shows hyperkeratosis, papillomatosis, slight irregular acanthosis, and keratin material formation. The neoplasm can produce the same qualitative changes in the subepithelial ECM on otherwise normal appearing skin. When the altered same epithelial changes occur on this biologically altered skin the result is many SK (the sign of Leser-Trélat).

Acanthosis Nigricans↗

PubMed1995

Matrix-assisted laser desorption ionization of neutral clusters composed of matrix and analyte molecules.

A new version of the matrix-assisted laser desorption ionization experiment is described. Composed clusters created by laser desorption of a mixture of analyte and matrix material were injected into a supersonic jet and then analyzed by multiphoton ionization time-of-flight mass spectrometry. Selective two-photon ionization of matrix molecules of a cluster component caused their dissociation, followed by intercluster proton or cation transfer to an analyte that is transparent for the wavelength of ionizing radiation. The intercluster charge transfer reactions are the only pathway for analyte ion formation under these conditions, as can be concluded from analysis of the mass spectra of a variety of substances.

Amino Acid Sequence↗

PubMed1996

Transmembrane-deletion mutants of the membrane-type matrix metalloproteinase-1 process progelatinase A and express intrinsic matrix-degrading activity.

Membrane-type matrix metalloproteinase-1 (MT-MMP-1) has been proposed to play a critical role in regulating the expression of tissue-invasive phenotypes in normal and neoplastic cells by directly or indirectly mediating the activation of progelatinase A. To begin characterizing MT-MMP-1 structure-function relationships, transmembrane-deletion mutants were constructed, and the processing of the zymogens as well as the enzymic activity of the mature proteinases was analyzed. We now demonstrate that pro-MT-MMP-1 mutants are efficiently processed to active proteinases following post-translational endoproteolysis immediately downstream of an Arg108-Arg-Lys-Arg basic motif by a proprotein convertase-dependent pathway. The secreted form of active MT-MMP-1 not only displays an N terminus identical with that described for the processed wild-type enzyme at Tyr112 (Strongin, A. Y., Collier, I., Bannikov, G., Marmer, B. L., Grants, G. A., and Goldberg, G. I. (1995) J. Biol. Chem. 270, 5331-5338), but also directly mediated progelatinase A activation via a two-step proteolytic cascade indistinguishable from that observed with intact cells. Furthermore, although the only function previously ascribed to MT-MMP-1 is its ability to act as a progelatinase A activator, purified transmembrane deletion mutants also expressed proteolytic activities against a wide range of extracellular matrix molecules. Given recent reports that MT-MMP-1 ectodomains may undergo intercellular transfer in vivo (Okada, A., Bellocq, J.-P., Rouyer, N., Chenard, M.-P., Rio, M.-C., Chambon, P., and Basset, P. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 2730-2734), our data suggest that soluble forms of the proteinase confer recipient cells with the ability to not only process progelatinase A, but also directly degrade extracellular matrix components.

Amino Acid Sequence↗

PubMed1997

The hemopexin-like domain (C domain) of human gelatinase A (matrix metalloproteinase-2) requires Ca2+ for fibronectin and heparin binding. Binding properties of recombinant gelatinase A C domain to extracellular matrix and basement membrane components.

The binding properties of the COOH-terminal hemopexin-like domain (C domain) of human gelatinase A (matrix metalloproteinase-2, 72-kDa gelatinase) were investigated to determine whether the C domain has binding affinity for extracellular matrix and basement membrane components. Recombinant C domain (rC domain) (Gly417-Cys631) was expressed in Escherichia coli, and the purified protein, identified using two antipeptide antibodies, was determined by electrospray mass spectrometry to have a mass of 25,925 Da, within 0.1 Da of that predicted. As assessed by microwell substrate binding assays and by column affinity chromatography, the matrix proteins laminin, denatured type I collagen, elastin, SPARC (secreted protein that is acidic and rich in cysteine), tenascin, and MatrigelTM were not bound by the rC domain. Unlike the hemopexin-like domains of collagenase and stromelysin, the rC domain also did not bind native type I collagen. Nor were native or denatured types II, IV, V, and X collagen, or the NC1 domain of type VII collagen bound. However, binding to heparin and fibronectin (Kd, 1.1 x 10(-6) M) could be disrupted by 0.58-0.76 and 0.3 M NaCl, respectively. Using nonoverlapping chymotrypsin-generated fragments of fibronectin, binding sites for the rC domain were found on both the 40-kDa heparin binding and the 120-kDa cell binding fibronectin domains (Kd values, approximately 4-6 x 10(-7) M). The Ca2+ ion, but not the potential structural Zn2+ ion, were found to be essential for maintaining the binding properties of the protein. The apo-form of the rC domain did not bind heparin, and both ethylenediaminetetraacetic acid and the specific Ca2+ ion chelator 1, 2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid, but not the Zn2+ ion chelator 1,10-phenanthroline, eluted the holo form of the rC domain from both heparin-Sepharose and fibronectin. Inductive coupled plasma mass spectrometry also did not detect a Zn2+ ion in the rC domain. In contrast, reduction with 65 mM dithiothreitol did not interfere with heparin binding, further emphasizing the crucial structural role played by the Ca2+ ion. Together, these data demonstrate for the first time that the hemopexin-like domain of gelatinase A has a binding site for fibronectin and heparin, and that Ca2+ ions are important in maintaining the structure and function of the domain.

Binding Sites↗

PubMed1997

Human thyroid carcinoma cell lines and normal thyrocytes: expression and regulation of matrix metalloproteinase-1 and tissue matrix metalloproteinase inhibitor-1 messenger-RNA and protein.

Matrix metalloproteinase-1 (MMP-1) and tissue matrix metalloproteinase inhibitor 1 (TIMP-1) play an important role in remodeling the extracellular matrix in normal and pathological processes. The effect of phorbol-myristate acetate (PMA), interleukin-1 (IL-1), and tumor necrosis factor-alpha (TNF-alpha) on MMP-1 and TIMP-1 expression was studied on highly purified thyrocytes and undifferentiated 8505 C, C 643, HTh 74, SW 1736 thyroid carcinoma cells compared with thyroid-derived fibroblasts. Messenger RNA (mRNA) levels were monitored by competitive semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) after 24 hours. Culture supernatants were assayed for free and/or complexed MMP-1 and TIMP-1 after 48 hours using enzyme-linked immunosorbent assay (ELISA) systems (detection limit: <2 ng/mL). MMP-1 and TIMP-1 mRNA were present in all cell types, although thyrocytes showed MMP-1 mRNA levels near the detection limit. 8505 C expressed MMP-1 mRNA levels of up to 10(6) times those of the other cells analyzed. PMA and IL-1 increased MMP-1 mRNA in most cell types. TIMP-1 mRNA increased after treatment with PMA in all cells except 8505 C, whereas only slight effects were shown after IL-1 stimulation. MMP-1 protein was undetectable in normal thyrocyte cultures, but was secreted spontaneously by all cell lines ([ng/mL]; C 643: 15+/-7; HTh 74: 81+/-1; SW 1736: 13+/-2; 8505 C: 2097+/-320). There was a strong correlation between levels of MMP-1 mRNA and protein (r = 0.99, p < .0001). PMA and IL-1 increased MMP-1 secretion in all cell types after 48 hours. Fibroblasts ([ng/mL] 517+/-55) and the cell lines (C 643: 142+/-48; HTh 74: 115+/-13; SW 1736: 202+/-14; 8505C: 120+/-19) secreted TIMP-1 in unstimulated cultures, whereas only a trace amount was detected in thyrocyte cultures, even after PMA treatment. IL-1 upregulated TIMP-1 secretion after 48 hours in SW 1736, HTh 74, and C 643 cells. Our data suggest that in contrast to normal thyrocytes, dedifferentiated thyroid carcinoma cell lines are potential producers of MMP-1 as well as TIMP-1. High MMP-1 or MMP-1/TIMP-1 expression may play a role in tissue invasion of undifferentiated thyroid cancer cells.

Adult↗

PubMed1993

Extracellular matrix. 2: Role of extracellular matrix molecules and their receptors in the nervous system.

Extracellular matrix molecules help regulate many aspects of neural development, including survival, migration, axon growth, and synapse formation by neurons. These same molecules have been shown to modulate regeneration of neurons after injuries. They also regulate the development and differentiation of other neural cells, such as astroglia and Schwann cells. Significant progress has been made recently in characterizing both ECM constituents and their receptors in the nervous system. Extracellular matrix molecules promote cell adhesion, activate intracellular signaling pathways, and modulate the activities of several growth factors and proteins. Our current understanding of the extracellular matrix, its receptors, and its functions in the nervous system are discussed.

Animals↗

PubMedDate not supplied

Synovial extracellular matrix II. Specific incorporation of immunoglobulin into the cell-free matrix of pannus.

To determine whether immune complex-like material is incorporated into the extracellular matrix (ECM) of proliferated RA synovium, cell-free matrices were isolated from pannus removed at joint replacement surgery, and were subjected to differential extraction. When the IgG and albumin concentrations in the ECM extracts were compared to those in simultaneously obtained synovial fluids, the IgG was found to be enriched 8.8-fold. Approximately 95% of the IgG was extractable with 6M Guanidine-HCl and 8 M Urea-B-ME. Further extraction with collagenase and low-pH buffers did not result in any additional recovery of IgG. Matrix-associated IgG demonstrated a restricted mobility on IEF with a pI of 4.8. The extracellular matrix of RA pannus is enriched in an acidic IgG species. Incorporation of IgG appears to be secondary to non-covalent interactions and may represent an additional reservoir of immune complex material in the rheumatoid joint.

Albumins↗

PubMed1993

Extracellular matrix production and degradation by adenoid cystic carcinoma cells: participation of plasminogen activator and its inhibitor in matrix degradation.

Adenoid cystic carcinoma (AdCC) is characterized by low mitogenic activity, high invasiveness, and vigorous production and accumulation of extracellular matrix (ECM). As it does in vivo, a cell line (ACCS) derived from a human AdCC grows very slowly and displays potential for production of a large amount of ECM. ACCS cells also produce a significant amount of proteolytic enzymes, including urokinase-type plasminogen activator (uPA), and M(r) 72,000 and 92,000 gelatinases. These cells can degrade considerable amounts of ECM elaborated by normal mesenchymal cells, including rat muscle cells and human fibroblasts, mainly through a uPA-plasmin cascade. However, ECM elaborated by ACCS cells themselves is resistant to degradation by either the tumor cells or purified uPA in the presence of plasminogen, whereas the degradation rates of ACCS ECM and mesenchymal ECM by plasmin are comparable. Treatment of ECM with glycine (pH 2.7), which removes plasminogen activator inhibitor from the matrix, results in an increase in the rate of ACCS ECM degradation by uPA. Moreover, fibrin agarose reverse zymography, autoradiography, and immunoblotting showed a high level of plasminogen activator inhibitor type 1 in ACCS ECM. These findings suggest that the plasminogen activator inhibitor type 1 in ECM produced by AdCC cells may play a role in preventing matrix destruction by the tumor itself, and thus the ECM components of tumor origin are stably accumulated in the intercellular spaces and may support or promote the growth of AdCC cells, which have primitively low growth activity.

Adenocarcinoma↗

PubMed1996

The solution structure of the bovine leukaemia virus matrix protein and similarity with lentiviral matrix proteins.

In the mature virion, retroviral matrix proteins are found in association with the inner face of the viral membrane. They play a critical role in determining the morphogenesis of virus assembly. We have determined the three-dimensional solution structure of the bovine leukaemia virus (BLV) matrix protein by heteronuclear nuclear magnetic resonance. The protein contains four principal helices that are joined by short, partially structured loops. Despite no sequence similarity with the lentiviruses, the structure shows an intriguing homology with the equivalent protein from the human and simian immunodeficiency viruses. A root-mean-square deviation of 3.78 angstrom is observed over the backbone atoms of 36 equivalent helical positions. The similarity implies a possible common assembly unit for the matrix proteins of type C retroviruses.

Amino Acid Sequence↗

PubMed1998

Activation of tumor cell matrix metalloproteinase-2 by neutrophil proteinases requires expression of membrane-type 1 matrix metalloproteinase.

BACKGROUND: Matrix metalloproteinase-2 (MMP-2), an enzyme involved in tumor invasion, is secreted as an inactive proenzyme and requires interaction with membrane-type 1 MMP (MT1-MMP) for activation. We have previously demonstrated that polymorphonuclear neutrophils (PMNs) release a soluble factor(s) that activates pro-MMP-2. Therefore, we tested the hypothesis that PMN-derived proteinases act in concert with MT1-MMP to activate pro-MMP-2. METHODS: Human HT-1080 cells transfected with MT1-MMP cDNA (HT-SE) or the corresponding antisense cDNA (HT-AS) or an empty vector (HT-V), which expressed differing levels of MT1-MMP, were incubated with serum-free, human PMN-conditioned medium with or without proteinase inhibitors. The culture supernatants were analyzed by gelatin zymography. RESULTS: Ht-1080 cells expressing basal (HT-V) or low levels (HT-AS) of MT1-MMP secreted MMP-2 in proenzyme from (72 kd). Ht-1080 cells with high levels of MT1-MMP (HT-SE) secreted pro MMP-2 and a 68 kd intermediate activation product. Addition of PMN-conditioned medium to either HT-SE or HT-V clones resulted in dose-dependent generation of active, 62 kd MMP-2. In contrast, when PMN-conditioned medium was added to HT-AS clones, no MMP-2 activation occurred. CONCLUSIONS: PMN-derived serine proteinases act in concert with MT1-MMP to activate proMMP-2. This finding indicates a potential role for inflammatory cells in promoting extracellular matrix breakdown during tumor invasion.

Aprotinin↗

PubMed1998

Coordinated and cell-specific regulation of membrane type matrix metalloproteinase 1 (MT1-MMP) and its substrate matrix metalloproteinase 2 (MMP-2) by physiological signals during follicular development and ovulation.

In the ovary, extensive tissue remodeling is required during both follicular development and the break down of the follicular wall at the time of ovulation. Extracellular proteases such as serine proteases and matrix metalloproteinases (MMPs) are thought to play pivotal roles in these processes. In this paper, we have used in situ hybridization to study the regulation and distribution of mRNA coding for MMP-2 (gelatinase A) and its cell surface activator membrane-type MMP1 (MT1-MMP) during gonadotropin induced ovulation in the rat. In ovaries of untreated immature (23 day old) rats, the levels of MT1-MMP and MMP-2 mRNA were low. MMP-2 mRNA was found in theca-interstitial cells while MT1-MMP mRNA was found in both granulosa and theca-interstitial cells and both messages were induced after stimulation with PMSG. After an ovulatory dose of hCG, the expression of MT1-MMP was dramatically down regulated in the granulosa cell layers of large preovulatory follicles but the expression remained and appeared to be up regulated together with MMP-2 in the theca-interstitial cells surrounding the large preovulatory follicles. The expression kinetics and tissue distribution supports the notion that MT1-MMP may have dual functions in the ovary. Initially MT1-MMP may act as a matrix degrading protease inside the follicle during follicular development and later, just prior to ovulation, as an activator of proMMP-2 in theca-interstitial cells surrounding preovulatory follicles.

Animals↗

PubMed1997

Imbalance of expression of matrix metalloproteinases (MMPs) and tissue inhibitors of the matrix metalloproteinases (TIMPs) in human pancreatic carcinoma.

Degradation of the extracellular matrix (ECM) is an essential step in tumour invasion and metastasis. The matrix metalloproteinases (MMPs) each have different substrate specificities within the ECM and are important in its degradation. MMP activity is dependent on the levels of activated MMP and tissue inhibitors of matrix metalloproteinases (TIMPs). The expression of MMPs and TIMPs in pancreatic carcinoma, normal pancreas, and pancreatic carcinoma cell lines has been determined by Northern analysis. The transcripts have been localized by in situ hybridization and the MMP2 protein by immunohistochemistry. Expression of MMP2, -7, and -11 was greater in pancreatic carcinoma than in normal pancreas (P < 0.01). MMP7 expression in normal pancreas and MMP7 and -11 expression in tumours was always seen the TIMP1 expression. TIMP2 was expressed in only half of the tumours and a previously undescribed transcript size is reported for TIMP2. MTMMP was expressed concurrently with MMP2 in 64 per cent of tumours, but concurrent MMP2 and TIMP2 expression occurred in only half. MMP2 mRNA was found more often in the tumour stroma than with the other MMPs or TIMPs (P < 0.02). It is concluded that while overexpression of MMP7 and -11 may be countered by TIMP1, the aggressive phenotype of pancreatic carcinoma may occur because of overexpression of MMP2, activated by MTMMP and associated with a reduced expression of TIMP2.

Blotting, Northern↗

PubMed1995

Conservative sorting of F0-ATPase subunit 9: export from matrix requires delta pH across inner membrane and matrix ATP.

In an attempt to understand the mechanisms of sorting of mitochondrial inner membrane proteins, we have analyzed the import of subunit 9 of the mitochondrial F1F0-ATPase (Su9) from Neurospora crassa, an integral inner membrane protein. A chimeric protein was used consisting of the presequence and the first transmembrane domain of Su9 fused to mouse dihydrofolate reductase (preSu9(1-112)-DHFR). This protein attains the correct topology across the inner membrane (Nout-Cin) following import. The transmembrane domain becomes first completely imported into the matrix, where after processing of the presequence, it mediates membrane insertion and export of the N-terminal tail. Import and export steps can be experimentally dissected into two distinct events. Translocation of the N-terminal hydrophilic tail out of the matrix was blocked when the presequence was not processed, indicating an important role of the sequences and charges flanking the hydrophobic domain. Furthermore, export was supported by a delta pH and required matrix ATP hydrolysis. Thus the hydrophobic transmembrane domain operates as a membrane insertion signal and not as a stop-transfer signal. Our findings suggest that several aspects of this sorting process have been conserved from their prokaryotic ancestors.

Adenosine Triphosphate↗

PubMed1993

Matrix-assisted laser desorption time-of-flight mass spectrometry of oligonucleotides using 3-hydroxypicolinic acid as an ultraviolet-sensitive matrix.

Matrix-assisted laser desorption time-of-flight mass spectrometry has been used to produce quasi-molecular ion signals from underivatized mixed-base single-stranded DNA oligomers ranging from 10 to 67 nucleotides in length. These results were obtained with a new matrix material, 3-hydroxypicolinic acid (3-hydroxypyridine-2-carboxylic acid) which showed significant improvement over many previously reported matrices studied in terms of mass range available, signal-to-noise ratio, and the ability to analyze mixed-base oligomers. The desorption and simultaneous ionization was by pulsed laser light at 10 to 50 mJ/cm2, studied at 266, 308, and 355 nm. Spectra taken at 266 nm provided the smallest amounts of doubly charged and dimer ions--characteristics desirable for DNA sequencing by this technology. Negative-ion spectra were uniformly superior to positive-ion spectra. This new matrix also is quite effective for molecular weight determinations of peptides and proteins in both positive- and negative-ion modes.

Base Sequence↗

PubMed1984

Induction of new proteins in the nuclear matrix of CHO cells by a heat shock: detection of a specific set in the nucleolar matrix.

An early response to an incubation of CHO cells for one hour at 43 degrees C is the appearance in the nuclear matrix of new proteins: 2 proteins (48 and 46 kDa) were associated with the extranucleolar part of the nuclear matrix, 6 other proteins (130, 100, 95, 85, 76 and 70 kDa) were present in matrices prepared from isolated nucleoli. In addition, a large increase in the amount of associated minor components is observed. It is suggested that these early modifications in composition of the matrix are related to the inhibition of rRNA and hnRNA synthesis and maturation.

Animals↗

PubMed1989

DNA fragments which specifically bind to isolated nuclear matrix in vitro interact with matrix-associated DNA topoisomerase II.

A matrix-associated region (MAR)-containing fragment has been selected from the library of cloned chicken nuclear matrix-associated DNA fragments. Factors, which determine the specific binding of DNA fragments have been studied. Using topoisomerase II-specific inhibitor VM 26 we established that nuclear matrix-associated topoisomerase II interacted with the MAR-containing DNA fragment producing specific cleavage sites on DNA of the fragment.

Animals↗