Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cellular interactions regulating the production of collagenase by a cell line derived from a spontaneously arising rat mammary carcinoma have been studied. The cell line, BC1, was grown permanently under defined serum-free conditions, so that the poorly characterized and variable effects of serum on collagenase expression were avoided. Two stable subpopulations of cells present in BC1 cultures were defined as epithelioid cells ("E-cells") and myoepithelioid cells ("M-cells"). These subpopulations differed in their morphology, pattern of growth and susceptibility to detachment from culture vessels by trypsin. Seven clones of M-cells and 7 clones of E-cells, obtained by the limiting dilution technique, were used to determine the cellular source of collagenase and the interactions which led to its expression. M-cells displayed an absolute dependence on a soluble factor produced by E-cells for their survival in vitro. The presence of both cellular types in culture was necessary for collagenase secretion to occur, E-cells being the major source of enzyme in mixed cultures. A soluble factor produced by M-cells was largely, if not completely, responsible for the induction of collagenase secretion by E-cells. Clones representative of both subpopulations were tumorigenic in syngeneic host animals. These results suggest that the phenotypic diversity which occurs within populations of neoplastic cells may give rise to subpopulations of cells which display a more aggressive phenotype in coexistence than in isolation.
 ...
PMID:Cellular interactions determining the production of collagenase by a rat mammary carcinoma cell line. 253 4

The modulation of the production of collagenase by an epithelial cell line derived from a spontaneously arising rat mammary carcinoma has been studied. The cell line, BC1, was grown permanently under defined serum-free conditions, thus avoiding the poorly characterized and variable effects of serum on collagenase production. Piperazine-N,N'-bis-(2-ethanesulfonic acid) (Pipes), retinoic acid and cytochalasin B all stimulated collagenase secretion, while dexamethasone inhibited it and progesterone, prolactin, prostaglandin E2, and estrogen had no effect. This profile of response to exogenous compounds was distinct from that of cells of mesenchymal origin and from human keratinocytes. For the production of large quantities of collagenase, culture medium was supplemented with Pipes (30 mM, pH 6.8), and retinoic acid (1 microM, on alternate feeds). The collagenase secreted by BC1 cells grown under these conditions was latent and had a molecular mass of 59 kDa. Treatment of the 59 kDa form with trypsin or APMA caused a progressive decrease in molecular mass via 54 kDa and 52 kDa intermediates, to a 48 kDa form. This form was purified to electrophoretic homogeneity by heparin-Sepharose, zinc-chelate-Sepharose, and Sephacryl S-200 chromatography. Five milligrams of purified collagenase were recovered per litre of culture medium.
 ...
PMID:The collagenase produced by neoplastic rat epithelial cells: modulation of secretion, molecular weight characteristics, and purification. 254 Apr 4

Cysteine proteinases, particularly cathepsins B and L, have been strongly implicated in fostering metastasis in mice. In this work four different inhibitors of cysteine proteinases have been shown to inhibit the invasion of the human amnion by murine melanoma and mammary carcinoma cells in vitro. Two of the inhibitors are synthetic peptides [ZPhePheCHN2 (benzyloxycarbonyl-L-phenylalanyl-L-phenylalanyldiazomethane) and ZPheAlaCH2F [3-(N-benzyloxycarbonylphenylalanylamido)-DL-1-fluoro-2-butanone]] and two are thiol protease inhibitors (TPIn, TPId) isolated from the skeletal muscle of the hind limbs of normal and dystrophic mice, respectively. The inhibitors (ZPhePheCHN2, TPId), with apparent selectivity for cathepsin L, blocked invasion as effectively as inhibitors (ZPheAlaCH2F, TPIn) effective on both cathepsins. The data reveal that in these cell lines the cysteine proteinases contribute significantly to the invasive capacity of the cells, but to a lesser extent than do the metalloproteinases. We suggest that the cysteine proteinases facilitate the action of metalloproteinases (collagenase, gelatinase, and stromelysin), possibly by activating them, by inactivating the tissue inhibitor of metalloproteinases, and/or by making basement membrane matrix more accessible.
 ...
PMID:Suppression by cathepsin L inhibitors of the invasion of amnion membranes by murine cancer cells. 273 Nov 77

A continuous line of human breast carcinoma cells, VHB-1, was established in culture following collagenase treatment of an infiltrating duct cell carcinoma. The cells displayed an epithelial pattern and multiplied rapidly. Maintained in monolayer culture, the VHB-1 cells exhibited a 30-h doubling time and a plating efficiency of 20%. The cells possessed an abnormal karyotype with a mode of 70-74 chromosomes per cell. The karyotype was heavily rearranged and numerous marker chromosomes were found. Transplantation of the cells into nude mice produced tumors bearing histological resemblance to the original material. The VHB-1 cells contained significant levels of prolactin receptors, were steroid hormone (estrogen, progesterone, androgen, glucocorticoid) receptor positive, and were capable of functional differentiation in vitro. These characteristics make the VHB-1 cell line a suitable model for studying the biological properties of human breast tumors.
 ...
PMID:Establishment and characterization of a new cell line (VHB-1) derived from a primary breast carcinoma. 282 20

To clarify interactions between carcinoma and mesenchymal cells, we examined the extracellular matrix-substance remaining on culture dishes after confluent growths of gastric carcinoma cells were removed with EDTA. The matrix synthesized by poorly differentiated adenocarcinoma cells (cell lines KATO-III and MKN-45) cultivated in serum-free medium has a fibroblast (cell line WI38)-attachment activity, which is not detected in the matrix synthesized by a well differentiated adenocarcinoma (cell line MKN-28). This activity was not observed in KATO-III-matrix extracted with 6 M urea, but could be detected in a 1% SDS extract from the remaining matrix on the culture dishes after 6 M urea extraction. The activity was abolished by treatment with pronase (16 micrograms/ml), trypsin (0.005%) or alkali, but was unaffected by collagenase (80 micrograms/ml, 4 h) or chondroitinase ABC (1 U ml, 1 h). It is conceivable that the fibroblast-attachment activity of the matrix produced by poorly differentiated adenocarcinoma cells is related to the proliferation of interstitial connective tissue in vivo.
 ...
PMID:Extracellular matrix of cultivated, poorly differentiated human gastric adenocarcinoma cells promotes attachment and spreading of mesenchymal cells. 290 Nov 69

An enzymatic method is described for disaggregation of viable tumor cells from human solid tumors. The enzymatic cocktail consists of 0.1% collagenase, 0.01% hyaluronidase, and 0.002% deoxyribonuclease. After mechanical mincing of the tumor tissue, tumor specimens are dissociated by incubation in the enzymatic cocktail for 12-18 hours at room temperature. In 17 cases of sarcoma, the mean yield was 5 X 10(6) viable cells per gram tumor tissue. Yield was 1 X 10(7) viable cells per gram tumor tissue in 23 cases of gastrointestinal carcinoma. The viabilities of tumor cell suspensions ranged from 50 to 98%, except for low viabilities in four specimens that were grossly composed almost entirely of necrotic tissue. The dissociation procedure is simple and the viable cell yield is sufficient for applications in studies of human cancer immunobiology.
 ...
PMID:An enzymatic method for the consistent production of monodispersed viable cell suspensions from human solid tumors. 298 62

Increased levels of peptidases are found in some human carcinomas and may be related to invasive potential. We therefore measured the activity of four peptidases in 50 specimens of tumour and normal colonic wall from patients with a rectal or sigmoid carcinoma, and correlated this with the stage, differentiation, fixity of the tumour and presence of venous invasion, determined histologically. Since acute phase reactant proteins (APRP) may inhibit these proteolytic enzymes we have also measured serum levels of two relevant APRPs, alpha 1 acid glycoprotein (AGP) and C-reactive protein (CRP) pre-operatively. Activity of cathepsin B, cathepsin H and collagenase-like peptidase (CLP) was determined fluorimetrically and collagenase photometrically. Significantly elevated activity of cathepsin B, CLP and collagenase was found in tumour compared with normal colonic wall (median values: (nmol (mg protein)-1 min-1) Cat B 0.71 and 0.42 (P less than 0.001), CLP 25.24 and 12.25 (P less than 0.0001) and collagenase 0.49 and 0.31 (P less than 0.001). There was no correlation between the activity of these enzymes expressed as a ratio of tumour/colonic wall, and differentiation or Dukes' stage of the tumour. However, there was significant elevation of activity of cathepsin B in tumours with local spread (n = 13) compared with those with no spread (n = 37) (median values 2.76 and 1.36 respectively (P less than 0.001] and also in tumour with venous invasion (n = 24) compared with tumours without (n = 26) (median values 1.82 and 1.18 respectively (P less than 0.01]. Pre-operative serum levels of CRP were inversely correlated with the activity of CLP and cathepsin H and collagenase in the tumours (rs = 0.332, 0.359 (P less than 0.05) and 0.302 (P = 0.05) respectively). Thus certain peptidases are raised in rectal and sigmoid tumours. Activity of cathepsin B appears related to local tumour invasion. APRP may have a role in inhibiting the activity of these enzymes. These findings may have therapeutic implications.
 ...
PMID:The role of peptidases in cancer of the rectum and sigmoid colon. 298 50

Lysis of type-I collagen by squamous carcinomas of the head and neck has been studied in freshly excised tissues, xenografts and established cell lines. Investigations with 35 freshly excised tumours showed only low levels of active and total collagenase in both carcinomas and controls. A difference became apparent when the tissues were set up in explant organ culture where a significant (p less than 0.05) increase in total collagenase was found in 13/19 tumours compared with paired control tissues over a 4-week culture period. Two xenografts showed little capacity to lyse collagen in vitro and there was only limited evidence of an increase in total collagenase after explantation and growth in organ culture. Twenty tumour cell lines showed low levels of active collagenase. Total collagenase levels were significantly increased (p less than 0.05) in 4 of the cell lines derived from cancers of the tongue; this activity was sustained in subsequent passages. Six control fibroblastoid cell lines also showed low levels of active collagenase. Levels of total collagenase were consistently high, but this activity was transient and declined in subsequent passages. Co-cultivation experiments with II tumour-cell lines and 5 fibroblastoid cell lines showed some enhanced, synergistic destruction of collagen. Parallel experiments with supernatant media from the carcinoma and fibroblastoid lines showed no enhancement, indicating that intact carcinoma cells and fibroblastoid cells are required for synergistic collagenolysis to take place.
 ...
PMID:Lysis of type-I collagen by squamous carcinomas of the head and neck. 299 Nov 44

The invasive RBTCC-8 rat bladder carcinoma cell line (passage number, greater than 100) and its derivates, the RBTCC-8 tumor isografts and the 1-RBTCC-8 daughter cell line (fourth passage), express proteolytic activities of broad substrate specificity, which allow them to efficiently degrade extracellular (collagenous) matrices. Cell-associated, collagenolytic activity is evidenced by the release of hydroxyproline from collagen substrates of types I and IV, by visualizing the low-molecular-weight collagen breakdown products on sodium dodecyl sulfate-polyacrylamide gels, and by the depth of invasion into extracellular matrices in our bone invasion assays. Fractionated by diethylaminoethyl column chromatography, the major collagenolytic activities against collagens of types I and IV coelute in a relatively narrow peak within a NaCl gradient. The pooled collagenolytic diethylaminoethyl fractions contain: (a) two chymotrypsin-like, catheptic activities; (b) activity against a synthetic elastase substrate; (c) gelatinase activity; and (d) caseinolytic activity. Despite efficient collagenolysis, a vertebrate-type collagenase cannot be detected in any of our tumor samples, even after trypsin activation of the tumor cell extracts. The mechanism of action of these nonspecific proteinases is thought to be that of collagen "crosslinkases." The neutral proteinase activities are highest in RBTCC-8 tumor isografts, intermediate in the fourth passage 1-RBTCC-8 carcinoma cell line, and lowest in the RBTCC-8 carcinoma cell line of high passage number. The levels of these nonspecific enzyme activities are well correlated with the depth of invasion into bony matrices, as shown by our invasion assays.
 ...
PMID:Connective tissue degradation by invasive rat bladder carcinomas: action of nonspecific proteinases on collagenous matrices. 300 15

The stroma of ductal infiltrating carcinoma of the human breast shows characteristic and localized areas of collagen rarefaction and fragmentation. This finding has been correlated with a peculiar type of fibrillar damage, observed in a small percentage of collagen fibrils isolated in the native state from the tumour stroma. The same pattern of lesion has been reproduced in vitro by human collagenase digestion on reconstituted fibrils. No effect has been detected by other nonspecific proteases in the same system.
 ...
PMID:Ultrastructural evidence of collagenolytic activity in ductal infiltrating carcinoma of the human breast. 303 10


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>