Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously purified from human placenta a basic fibroblast growth factor (FGF)-like molecule which stimulates the production of plasminogen activator (PA) and collagenase, induces DNA synthesis, produces an increase in motility in cultured bovine capillary endothelial (BCE) cells, and induces angiogenesis in vivo. The ability of basic FGF to stimulate PA production in BCE cells was used as an assay for the presence of basic FGF-like molecules in extracts of both normal and tumor-derived cultured cells. The identity of the PA-stimulatory activity with basic FGF was confirmed by its high affinity for heparin and by its cross-reactivity with antibodies to human placental basic FGF. Basic FGF-like molecules were identified in eight of ten cell lines tested, and the amount of FGF-like activity present in these cells bore no relation to their origin from normal or tumor tissue. The test cells, BCE cells, had one of the highest levels of FGF-like activity, suggesting that it may have an autocrine role in these cells.
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PMID:Both normal and tumor cells produce basic fibroblast growth factor. 302 87

To understand the role of proteinases in tumor invasion, the effects of inhibitors of metallo-, serine-, and cysteine-proteinases on this process were studied using 125I-iododeoxyuridine-labeled B16/BL6 cells grown on human amnion basement membrane. Cellular invasion was quantitated by measuring the radioactivity associated with the amniotic membrane after the B16/BL6 cells on the basement membrane were removed by lysis followed by scraping. The results obtained with proteinase inhibitors showed that inhibitors of collagenase and plasmin prevented invasion of the amnion. Tissue invasion was also blocked by antiurokinase antibodies. On the contrary, cysteine-proteinase inhibitors and anti-tissue plasminogen activator antiserum were ineffective. Mersalyl, a compound known to activate collagenase, stimulated invasion under conditions where plasmin formation or activity were inhibited. Evidence for the role of a plasminogen activator-plasmin-collagenase activation cascade in B16 invasion is provided.
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PMID:Tumor invasion through the human amniotic membrane: requirement for a proteinase cascade. 302 33

A 17,500-dalton protein which stimulates plasminogen activator production in cultured bovine capillary endothelial cells has been purified from a SK-Hep-1 human hepatoma cell lysate by using heparin affinity chromatography and fast protein-liquid ion exchange chromatography. The purified molecule stimulated plasminogen activator production in a dose-dependent manner between 0.01 and 1 ng/ml. It also stimulated collagenase synthesis, DNA synthesis, and motility in capillary endothelial cells in the same concentration range. This molecule was identified as a basic fibroblast growth factor-like molecule on the basis of its biological activity, its affinity for heparin-Sepharose, and its cross-reactivity with a polyclonal antibody raised against the human placental basic fibroblast growth factor.
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PMID:Purification from a human hepatoma cell line of a basic fibroblast growth factor-like molecule that stimulates capillary endothelial cell plasminogen activator production, DNA synthesis, and migration. 302 28

The tumorigenic properties of human rheumatoid arthritis synovial cells in culture were investigated. The synovial cells developed good colonies and secreted plasminogen activator (PA) and collagenase in the cell cultures, as do Hela cells. Since PA and progesterone receptor (PgR) are considered to be end products of estradiol action in breast cancer cells, the estrogen receptor (ER) and PgR content in these cells was also assayed. Large amounts of ER and PgR were detected in the synovial cells in culture, even though these cells are not targets for sex steroids. Study of the cytomorphologic changes in the synovial cells in culture revealed many characteristics generally observed in neoplastic cells. Whether any or all of these observations have any implication in prognosis or therapy in this disease remains to be studied.
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PMID:Expression of tumor cell properties in synovial cells in culture. 302 23

Activated ras oncogene transfection into suitable recipient cells has been shown to induce the metastatic phenotype (Thorgeirsson, et al., Mol. Cell. Biol., 5: 259-262, 1985). We have used this model system to study the correlation of basement membrane collagenolysis with metastatic propensity. The c-Ha-ras oncogene alone, or combined with v-myc, transfected into early passage rat embryo fibroblasts, induce these cells to secrete high levels of type IV collagenolytic metalloproteinase and to concomitantly exhibit a high incidence of spontaneous metastases in nude mice. Cotransfection of c-Ha-ras plus the adenovirus type 2 E1a gene yields cells which are highly tumorigenic but nonmetastatic and fail to produce type IV collagenase. This effect is due to a suppression of collagenase elaboration, not increased production of a collagenase inhibitor, and not decreased production of a collagenase activator. The characteristics of the collagenase are identical to tumor type IV collagenase described previously. The nonmetastatic cells which failed to produce type IV collagenase retain the ability to secrete high levels of plasminogen activator. Transfection with the protooncogenic forms of Ha-ras or mos, or spontaneous transformation of NIH 3T3 cells or chemical transformation of BALB 3T3 cells yields cells which fail to produce collagenase, are tumorigenic, but totally nonmetastatic. These data support a biochemical linkage of type IV collagenase expression with the metastatic phenotype in this rodent system.
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PMID:Secretion of type IV collagenolytic protease and metastatic phenotype: induction by transfection with c-Ha-ras but not c-Ha-ras plus Ad2-E1a. 302 10

During ovulation, enzymatic degradation of the extracellular matrix occurs within and around the graafian follicles. In this study, the activities of several different proteolytic enzymes were measured in the culture media of follicles taken from pregnant mare serum gonadotropin (PMSG)-primed immature rats. At 52 h after PMSG, the follicles were cultured for 2 to 15 h in media with or without human chorionic gonadotropin (hCG). Type I collagenase activity in hCG-stimulated follicles gradually increased within 6 h to 3.3-fold above that of the controls. Relatively pure populations of granulosa cells produced type I collagenase to a similar extent. Likewise, type IV collagenase increased 3.8-fold by 6 h after exposure of the follicles to hCG. In contrast, plasminogen activator activity increased by 3.9-fold at 2 h after hCG, but was negligible at 4, 6, and 15 h after incubation. These results suggest that plasminogen activator may activate both type I and type IV collagenase in hCG-stimulated ovulatory follicles.
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PMID:Types I and IV collagenolytic and plasminogen activator activities in preovulatory ovarian follicles. 303 95

A new method for isolation and culture of endothelial cells from bovine coronary artery (BCoAEC) is presented. This method involves in situ perfusion and digestion of main coronary arteries with a collagenase solution. The isolated cells were cultured and maintained through many cell passages in Dulbecco's Modified Eagle's Medium supplemented with fetal bovine serum derived from either whole blood or plasma. Confirmation of these cells' endothelial origin was obtained by demonstration of typical morphologic and growth characteristics of endothelium, immunofluorescent staining with antibodies to von Willebrand factor (Factor VIII: vWF), and measurement of plasminogen activator (PA). In addition, production of PA was inhibited by enzymatically active thrombin as has been previously described with bovine aortic endothelial cells in culture.
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PMID:Bovine coronary artery endothelium: in vitro culture and production of plasminogen activator. 308 24

A cell culture model has been established employing normal human articular or costal chondrocytes in monolayer culture as target cells for the effects of intercellular mediators on chondrocyte function, particularly collagen synthesis. Recombinant Interleukin-1 (IL-1) which stimulates the synthesis of prostaglandin E2 (PGE2), collagenase, and plasminogen activator also stimulates the synthesis of collagen and increases steady-state levels of mRNA in cultured chondrocytes, synovial cells and foreskin fibroblasts if the synthesis of PGE2, which inhibits collagen synthesis, is inhibited by indomethacin. Recombinant immune interferon (IFN-gamma), which does not affect collagenase of PGE2 production, suppresses type II as well as types I and III collagen synthesis and associated mRNA levels. IL-1 and IFN-gamma could therefore have opposite roles in modulating cartilage matrix turnover in joint disease by affecting repair as well as degradation.
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PMID:Control of collagen synthesis in human chondrocyte cultures by immune interferon and interleukin-1. 311 88

The correlation between proteinase activities and invasive and metastatic potentials was investigated by comparing three different kinds of tumors. Extracts from tumor homogenate of 11 squamous cell carcinoma (SCC), 5 basal cell epithelioma (BCE), and 8 seborrheic keratosis (SK) were prepared in order to examine the activity of acid phosphatase and proteinases such as cathepsin B and D, type I and IV collagenase, and plasminogen activator (PA). There was no difference observed between acid phosphatase and cathepsin D activities among the three tumors. Cathepsin B and PA activities were slightly elevated in SCC. Type I collagenase activity of SCC was 9-fold higher than that of SK (p less than 0.01), and type IV collagenase was 3-fold higher per tissue DNA (p less than 0.05). Type I and IV collagenase of BCE were elevated per tissue protein but not elevated per tissue DNA. Correlation was found between the level of cell differentiation in SCC and the activities of cathepsin B, PA, and type I collagenase. Poorly differentiated SCC exhibited a tendency to have higher proteinase activities. Proteinases that showed high activities in malignant tumor homogenate may be related to the degradation of the surrounding cell matrix in addition to intracellular metabolism. Type I and IV collagenase, in cooperation with cathepsin B and PA, might play a major role in invading the dermal stroma and basement membrane.
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PMID:Comparison of proteinase activities in squamous cell carcinoma, basal cell epithelioma, and seborrheic keratosis. 328 80

In an attempt to understand the mechanism by which estrogens stimulate cell proliferation and mammary carcinogenesis, metastatic human breast cancer cell lines (MCF7, ZR75-1) were found to secrete a 52,000 dalton (52K) protein under estrogen stimulation. Following its purification to homogeneity, the 52K protein was identified as a secreted procathepsin-D-like aspartyl protease bearing mannose-6-phosphate signals. This precursor displays an in vitro autocrine mitogenic activity on estrogen-deprived MCF7 cells and is able to degrade basement membrane and proteoglycans following its autoactivation. The total protease (52K + 48K and 34K) was detected and assayed by monoclonal antibodies and was found to be highly concentrated in proliferative and cystic mastopathies. In breast cancer, its cytosolic concentration appears to be correlated more to tumor invasiveness than to hormone responsiveness. The mRNA of the 52K protease accumulates rapidly following estradiol treatment, as was shown by Northern blot analysis with cloned cDNA. The 52K cathepsin-D-like protease is the first example of a lysosomal protease induced by estrogens in cancer cells. Results obtained using different approaches suggest that two cysteinyl cathepsins are also related to cell transformation and invasiveness. It has been proposed that cathepsin-B is involved in breast cancer and metastatic melanoma, and its regulation by estrogen has been shown in the rat uterus. Cathepsin-L corresponds to the major excreted protein (MEP) whose synthesis and secretion are markedly increased by transformation of NIH 3T3 cells with Ki ras and are regulated by several growth factors. In addition to secreted autocrine growth factors and to other proteases (plasminogen activator, collagenase), lysosomal cathepsins may therefore play an important role in the process of tumor growth and invasion as long as their precursor is secreted abundantly.
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PMID:Estrogen-induced lysosomal proteases secreted by breast cancer cells: a role in carcinogenesis? 331 45


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