Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An inhibitor of plasminogen activator (PA) secreted by a tumorigenic, but non-metastatic, rat mammary adenocarcinoma cell line has been purified to apparent homogeneity and characterized. It strongly inhibited human urokinase, but was 100 times less potent in inhibiting bovine trypsin and had no effect on plasmin or thrombin. A secreted, urokinase-type PA (Mr 48 000) and a cell-associated PA from a metastatic rat adenocarcinoma cell line were also strongly inhibited. In contrast, a tissue-type PA (Mr 66 000), secreted by human melanoma cells, was only slightly inhibited. Purified inhibitor showed a band of Mr 66 000 in sodium dodecyl sulphate/polyacrylamide gel electrophoresis and an isoelectric point of 4.5 after chromatofocusing. The inhibition of human urokinase was non-competitive.
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PMID:Purification and characterization of an inhibitor of plasminogen activator released by rat mammary adenocarcinoma cells. 308 43

A large fraction of colonic epithelial cells (45 +/- 15%) formed rosettes with sheep red blood cells (RBC) but not with bovine or human RBC. This interaction was independent of the T11 receptor since it was not inhibited by anti-T11 antibody or trypsin treatment of the epithelial cells. The binding was also not due to surface immunoglobulin reactive with sheep RBC since antibodies to immunoglobulin light chains did not block the interaction. Sheep RBC rosettes formed around colonic and jejunal epithelial cells, a few percent of colonic adenocarcinoma cells, but not around uterine epithelial cells. Sheep RBC rosette formation should not be used to quantitate or isolate intestinal mucosal T cells if epithelial cells are present.
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PMID:Intestinal epithelial cells rosette with sheep red blood cells. 308 24

The human adenocarcinoma cell line HT 29 grows virtually without tight junctions, but the formation of focal tight junctions can be induced by brief treatment with proteinases. The freeze-fracture morphology of proteinase-induced tight junctions is not affected by treatment with EGTA or EDTA over a period of 30 min. The induction of tight junctions by trypsin or pronase can proceed in the presence of 3 mM EGTA or EDTA. Neither the formation nor the structure and complexity of the induced tight junctions is affected by the chelators. It follows that no extracellular divalent cations are required for the induced formation and the structural integrity of focal tight junctions in HT 29 cells.
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PMID:Proteinase-induced formation of focal tight junctions in HT 29 adenocarcinoma cells does not require extracellular calcium. 311 54

A murine monoclonal antibody (MAb), PA 8-15, was produced against a newly established human pancreatic adenocarcinoma cell line, SUIT-2. With the avidin-biotin immunoperoxidase technique, PA 8-15 MAb reacted strongly with 27 of 28 formalin-fixed paraffin-embedded pancreatic adenocarcinoma tissues. All six gall bladder carcinomas and all nine biliary tract carcinomas also showed positive reactions. In addition, PA 8-15 MAb reacted with gastric carcinomas (6/10), colorectal carcinomas (7/11), and some other primary adenocarcinomas. The distribution of PA 8-15 antigen on the same tissues of pancreatic cancer was different from those of CA 19-9 and DU-PAN-2 antigens and CEA. PA 8-15 MAb stained only the epithelium of the pancreatic duct, gall bladder and bile duct in normal adult tissues, and some normal fetal glandular epithelial cells. However, PA 8-15 MAb was not reactive with inflammatory or benign tumors of the digestive system except for the epithelium, as was seen in normal adults. Reactivity of PA 8-15 MAb with tissue specimens largely disappeared after treatment with neuraminidase, while oxidation with periodate or trypsin digestion did not alter the staining intensity, indicating that antigenic determinants may be at least partly of sialylated carbohydrate nature. These results suggest that PA 8-15 MAb detects a new oncofetal antigen in gastrointestinal cancers, especially of the pancreatico-biliary tract.
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PMID:Immunohistochemistry of human gastrointestinal cancer-associated antigen detected by monoclonal antibody PA 8-15. 313 Mar 61

A glycopeptide from adenocarcinoma tissue of human lung was extracted by protein digestion with papain (EC 3.4.22.2) and trypsin (EC 3.4.21.4). This component was isolated by Pevikon block electrophoresis. It possessed hexose, glucosamine, fucose, galactosamine, and sialic acid. In its carbohydrate composition and also the abundance of threonin in the peptide moiety it was quite similar to the glycoprotein from gastrointestinal tract. The physical characteristic of the two, such as their optical rotation and viscosity, were also very similar each other.
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PMID:A glycopeptide from adenocarcinoma tissue of human lung. 321 27

A cell line designated SNG-II was established from the operation specimen of human endometrial adenocarcinoma, and by means of an immunization procedure using intact SNG-II cells, a monoclonal antibody (Mab) named MSN-1 which reacts immunohistochemically with endometrial cancers was obtained. The cell line grew well without interruption for over 5 years, and, SNG-II cells produced tumors of cell differentiated adenocarcinoma in nude mice. The modal chromosomal number was diploid without a marker chromosome. The production of human chorionic gonadotropin and its beta-subunit, CA-125, tissue polypeptide antigen, and placental proteins such as PP6 and PP7 in SNG-II was confirmed. MSN-1 was of IgM subclass. As the antigenic reactivity was unchanged by trypsin treatment, but lost by periodic treatment, it was suggested that the antigen corresponding to MSN-1 was a carbohydrate sequence. Immunohistochemically MSN-1 reacted with about 70% cases of endometrial adenocarcinoma, but seldom with normal endometrium. Furthermore, the staining pattern of MSN-1 was different in benign cells from that in malignant cells: only the luminal surface of the normal endometrium was positive, whereas the cytoplasma was also stained in many of adenocarcinoma cells.
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PMID:[Production of monoclonal antibody against a newly established human endometrial cancer cell line SNG-II]. 329 79

Pancreatic secretory trypsin inhibitor (PSTI) immunoreactivity was detected by a radioimmunoassay in a serum-free culture medium conditioned by a human pancreatic adenocarcinoma cell line, CAPAN-1. Its apparent rate of secretion was 280 +/- 20 fg/cell/24 h, and increased in the presence of fetal bovine serum, but was not affected by a cell density at an early stage of culture. This PSTI immunoreactivity was indistinguishable from authentic human pancreatic PSTI on gel filtration, immunoblot analysis and trypsin affinity chromatography.
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PMID:Pancreatic secretory trypsin inhibitor immunoreactivity detected in serum-free culture medium of human pancreatic carcinoma cell line, CAPAN-1. 335 13

The human colon adenocarcinoma cell line HT 29 grows virtually without tight junctions (TJ) under standard culture conditions. Earlier studies have shown that focal TJ (fasciae occludentes) can be rapidly assembled in this cell line under the influence of various proteases. Here we show that focal TJ can be induced in this cell line by a brief treatment with appropriate salt solutions. Induction by ammonium sulfate in Hanks' buffer reached a maximum value after 15 to 30 min. The amount of TJ increased with the salt concentration and reached a plateau value at a concentration of 160 mM ammonium sulfate. The amount and complexity of TJ induced by ammonium sulfate were similar to those in experiments using trypsin as inducing agent as shown by morphometric analysis. At 0 degrees C, no TJ were formed under the influence of the salt. A comparative study of TJ induction using a variety of inorganic and organic salts gave the following results. All alkali sulfates induced TJ, although with different yield. Both calcium and magnesium chloride were potent inducers. Ammonium and sodium salts encompassing a variety of anions covered a wide range from maximum induction (sulfate, citrate) to almost complete absence of induction (nitrate). Sodium chloride did not induce any TJ. It follows that the induction of TJ is a specific effect of individual ionic components of the solution as opposed to a general effect of osmolarity and ionic strength. The data suggest tentatively that antichaotropic but not chaotropic ions have the potential to trigger the formation of TJ in this experimental system.
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PMID:Rapid formation of tight junctions in HT 29 human adenocarcinoma cells by hypertonic salt solutions. 339 Dec 41

Serum-free culture medium conditioned by an established human pancreatic adenocarcinoma cell line, CAPAN-1, contains copious amounts of immunoreactivity due to pancreatic secretory trypsin inhibitor (PSTI) as demonstrated by radioimmunoassay. The immunoreactive substance was purified from the conditioned medium to apparent homogeneity by trypsin affinity and gel filtration chromatography with an overall recovery of 40%, and its primary structure was determined by Edman degradation. The immunoreactive substance is a peptide of 56 amino acid residues with a calculated molecular weight of 6,241. Its amino acid composition, primary structure, and inhibitory effect against trypsin are indistinguishable from those of human pancreatic juice PSTI, indicating that this substance is PSTI itself. This is the first direct demonstration that tumor cells secrete PSTI in vitro. When CAPAN-1 was inoculated into a nude mouse, it produced a tumor and the tumor synthesized human PSTI in vivo, as demonstrated by the fact that the tumor extract contained 99.0 +/- 26.2 ng of human PSTI/mg of protein, while PSTI was not detected in extracts from other tissues examined. Furthermore, high levels of human PSTI (14.3 +/- 2.6 ng/ml) were detected in the serum of tumor-bearing mice but not in that of nontumor-bearing mice, suggesting that PSTI secreted from the tumor appears in the blood circulation. Taken together, these results strongly support the view that the serum levels of PSTI are elevated in cancer-bearing patients due to secretion of this peptide from tumor cells per se.
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PMID:Demonstration of pancreatic secretory trypsin inhibitor in serum-free culture medium conditioned by the human pancreatic carcinoma cell line CAPAN-1. 341 64

Demineralized extracts of bone matrix and conditioned media from cultured fetal rat calvaria have been reported to contain growth stimulatory activity for bone cells. To investigate the potential role of these local bone growth factors in the development of bone metastases, we chose the Walker 256 carcinosarcoma, a rat mammary tumor which causes osteolytic bone metastases and hypercalcemia. 45Ca-labeled, 19-day fetal Sprague-Dawley rat calvaria were cultured for 96 hours in BGJb medium. Walker cells from ascites tumors or cultures were grown in unconditioned media or in conditioned media harvested from the bone cultures, in the presence of 10% fetal calf serum. Media were changed every 2 days, cells were counted daily for 5 days, and 3H-thymidine uptake into acid insoluble residues was measured. The growth of tumor cells was 5-6-fold greater in conditioned media than in unconditioned media and the effect was dose dependent. Cells cultured in conditioned media demonstrated a approximately 3-fold enhancement of 3H-thymidine incorporation. Generation of growth stimulatory activity correlated with the extent of bone resorption, measured by release of 45Ca from the fetal parietal bones (r = 0.85; P less than 0.001). Conditioned media from bones cultured with 10(-7) M prostaglandin E2 (PGE2) contained greater amounts of growth stimulatory activity than untreated conditioned media, but PGE2 itself did not stimulate tumor cell growth. Addition of 3.5 mM PO4 to bone cultures blocked bone resorption and the generation of growth factors. Growth stimulatory activity was stable to heat (56 C for 30 minutes) and trypsin digestion, with an apparent molecular weight of less than 17,000 daltons by high-performance liquid chromatography. Conditioned medium also stimulated the growth of 13762 rat mammary adenocarcinoma cells, MB-MDA-231 human breast carcinoma cells, TE-85 osteosarcoma cells, a murine fibrosarcoma and rat embryonic fibroblasts, with the most potent effects noted for Walker tumor cells, the TE-85 osteosarcoma, and human breast carcinoma lines. These results suggest a mechanism by which bone resorption could promote the development of skeletal metastasis.
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PMID:Resorbing bone stimulates tumor cell growth. A role for the host microenvironment in bone metastasis. 345 36


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