Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case of ceruminous adenocarcinoma is reported. The tumor destroyed the right pyramid, widely invaded the base of the skull and caused death shortly after the diagnosis. Distant metastases were not found by autopsy. The tumour cells reacted with epithelial markers and with the antibody against S-100 protein. Heparan sulphate proteoglycan seemed to be a good marker for detecting basement membrane ruptures and concomitant tumour invasion. Among the lectins BS-I and PNA gave the strongest reactions in the stroma. This is the first immunohistochemical and lectin histochemical report on ceruminous adenocarcinoma.
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PMID:Adenocarcinoma of ceruminous glands. Ultrastructural, immunohistochemical and lectin histochemical studies. 178 46

Cryopreserved cell suspensions of freshly excised melanoma metastases from nine patients were injected s.c. into C.B-17 severe combined immunodeficiency (SCID) mice. All 9 tumors grew as s.c. masses and six of nine were successfully transplanted into other SCID mice. Transplant inocula as low as 5 x 10(5) cells resulted in 100% tumor incidence. Moreover, seven of nine tumors metastasized, five from the original s.c. implants and two from transplanted s.c. tumors. Metastases were detected mainly in the lungs but also were found in abdominal viscera (liver, spleen, and pancreas) and thoracic lymph nodes. Flow cytometric analysis showed that expression of a panel of melanoma antigens, melanoma-associated proteoglycan, ganglioside GD3, and ganglioside GD2, was maintained with SCID passage. The original tumor inocula contained a variable percentage of tumor-associated lymphocytes (1-76%). Flow cytometry analysis indicated that these were mainly CD3+ T-cells. However, there was no correlation between the percentage of tumor-associated lymphocytes and the time required for development of a palpable tumor after s.c. injection or the ability to metastasize. These results demonstrate the growth and spontaneous metastasis of fresh human melanoma in SCID mice and suggest that this model could be important for therapeutic and basic biological studies.
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PMID:Growth and metastasis of fresh human melanoma tissue in mice with severe combined immunodeficiency. 189 83

In vitro cancer studies require models more appropriate than the standard monolayer cultures of tumoral cell lines. This report describes the production of an in vitro three-dimensional rebuilt tumor using a non-hodgkin malignant lymphoma. The model exploits the relationship between angiogenesis and cancer formation by employing both tumor cells and fusiform cells derived from an angioma. The significance of this model, which has also been used with malignant melanoma cells, is that the rebuilt tumor, when placed in culture, produces many tumorous nodules which are fixed to a sub-layer of fusiform cells and newly-secreted matrix. These are, in effect, in vitro metastases. The ultrastructural aspect of this neomatrix indicates its proteoglycan nature. The micro-environment formed by the vascular cells and matrix appears to be critical for the production of metastases.
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PMID:[Three-dimensional model of cancer and in vitro metastasis: application to non-Hodgkin malignant lymphoma]. 191 48

The functional properties of the melanoma-associated antigens detected by monoclonal antibodies (MAbs) AMF-6 and AMF-7 were investigated. These MAbs were selected previously because of their capacity to block the anti-melanoma reactivity of cytotoxic T-lymphocyte clones AMF-6 and AMF-7 detect a melanoma-associated proteoglycan (MW greater than 450-250 kDa) and a molecular complex, which under reducing conditions consists of 4 compounds of 120, 95, 29 and 25 kDa respectively. AMF-6 reacted strongly with all 30 cultured melanomas and all 41 melanomas in frozen tissue sections. Significant cross-reactivity was only observed with nevi and perineurium, whereas normal skin melanocytes were negative. AMF-7 reacted with all 25 cultured melanomas and all 34 melanomas in frozen sections. AMF-7 cross-reacted with a proportion of nevi and endothelial cells from small vessels. The antigen detected by AMF-6 and AMF-7 could not be modulated by retinoic acid or recombinant gamma-IFN, which induced or enhanced the expression of HLA-DR, HLA-DQ and Class-I MHC antigens. In addition, the antigens were not readily modulated when cells were incubated in excess amounts of AMF-6 and AMF-7. Interestingly, the antigen detected by AMF-7 was strongly associated with the adhesion and cytoplasmic spreading of melanoma cells to plastic surfaces and monolayers of vascular endothelial cells. AMF-6 did not block the adhesion of melanoma cells but delayed cytoplasmic spreading. Both AMF-6 and AMF-7 blocked fibronectin-induced chemotaxic motility and chemokinesis of melanoma cells. In addition to their membrane localization, the antigens detected by AMF-6 and AMF-7 were also abundant in extracellular adhesion plaques deposited by cultured melanoma cells. Our results indicate that the high-MW melanoma-associated proteoglycan and the antigen detected by AMF-7 are associated with adhesion and/or cytoplasmic spreading and motility of human melanoma cells, suggesting that these antigens are associated with the (hematogenic) dissemination of human melanoma. This is supported by the finding that AMF-7 stained primary tumors heterogeneously, whereas metastases were homogeneously stained.
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PMID:Characterization of melanoma-associated surface antigens involved in the adhesion and motility of human melanoma cells. 242 58

The goal of this study has been to identify and characterize metalloproteinases from a highly metastatic human small cell lung cancer cell line. The cytosol isolated from NCI-H82 lung cancer cells propagated as solid tumors in nude mice contained a gelatinolytic enzyme that was subjected to ammonium sulfate precipitation, zinc chelate Sepharose column chromatography, anion exchange chromatography and gel permeation chromatography. This purification scheme resulted in a 280-fold enrichment of an active gelatin and type IV collagen-degrading enzyme. On gelatin zymography two bands of gelatinolytic activity were detected, corresponding to Mr of 75,000 and 63,000. Gelatinolytic activity was inhibited by metal chelators, tetracyclines, and serum. On immunoblotting using an affinity-purified polyclonal rabbit antibody to a peptide region of type IV collagenase, the tumor enzyme was identified as type IV collagenase. A second tumor metalloproteinase of Mr = 29,000, which degraded proteoglycan substrates, was also isolated.
Invasion Metastasis 1989
PMID:Gelatin-degrading type IV collagenase isolated from human small cell lung cancer. 254 76

We used flow cytometry to measure the expression of human melanoma antigens on cell suspensions dissociated from metastatic masses. The objective was to study the heterogeneity between tumor samples from different patients and between different tumors excised from a single patient. Fifty-three metastases excised from 34 melanoma patients were analyzed with a panel of nine murine monoclonal antibodies (MOABs). Melanoma cells were stained by an indirect fluorescent method and analyzed on a Coulter EPICS C flow cytometer after gating to exclude tumor-infiltrating leukocytes and dead cells. The most consistently and most strongly expressed antigen was the high-molecular-weight proteoglycan (detected by the MOAB 9.2.27), which was expressed on 95% of the melanoma specimens and by a high proportion of cells within each specimen (mean +/- SE, 79.2 +/- 5.5). However, strong expression of this antigen was limited to melanoma cells that had been dissociated mechanically and was markedly diminished by exposure to collagenase. Culture of collagenase-dissociated tumor cells for 24 to 48 h resulted in reexpression of the antigen. The expression of other melanoma-associated antigens was not affected by collagenase treatment, but for these antigens there was more variability between cells from an individual tumor and between tumors from different patients. The percentage of enzyme-dissociated tumors considered positive for MOAB binding (defined as at least 10% of cells positive) and the mean +/- SE of the percentage of positive cells within a tumor were as follows: MOAB ME-9-61 (antigen, p97) = 84% + (41.2 +/- 5.4%); MOAB ME-20.4 (antigen, nerve growth factor receptor) = 40% + (18.7 +/- 5.1%); MOAB ME-24 (antigen, ganglioside GD3) = 84% + (50.8 +/- 4.8%); MOAB ME-311 (antigen, ganglioside 9-O-acetyl-GD3) = 76% + (42.5 +/- 5.1%); MOAB ME-361 (antigen, mainly ganglioside GD2) = 3% + (1.9 +/- 0.8%); MOAB 3F8 (antigen, ganglioside GD2) = 36% (10.5 +/- 3.8%); MOAB 14G2a (antigen, ganglioside GD2) = 86% + (46.0 +/- 6.7%); MOAB L243 (antigen, HLA-DR) = 56% + (22.5 +/- 5.5%). In 19 cases, we were able to compare the antigenic profiles of two tumors excised from the same patient at different times. Analysis by nonindependent t test showed no significant differences in MOAB binding between the paired tumors. Moreover, linear regression analysis indicated that there was a linear relationship, with a slope approximately = 1, between the percentage of positive cells in Tumor 1 versus Tumor 2.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Flow cytometric determination of the frequency and heterogeneity of expression of human melanoma-associated antigens. 258 30

A new technique was developed to coat Nuclepore filters with basement membrane matrix components. Using the EHS tumour as a source, a proteoglycan and laminin-containing fraction was extracted with guanidine and collagen type IV was solubilized in a second fraction by limited digestion with pepsin. When the two fractions are combined and guanidine removed by dialysis, a gel is rapidly formed. A flat-bed dialysis apparatus was devised, allowing gels to form on filters that are soaked in the mixture, thus coating them with components of the basement membrane. Such filters were used for selection of B16 melanoma cells penetrating the gels. 10 clones were isolated after three selection passages, and assayed for spontaneous metastasis in C57Bl/6 mice after intracutaneous injection. The metastasis rates were strongly increased to the lungs and to inguinal and axillary lymph nodes. Less accessible sites such as mediastinal and maxillary lymph nodes were reached only by selected cells. There was no particular preference for the haematogenous or lymphatic routes, indicating that the ability to traverse the basement membrane leads to a general increase of metastasis. The described method provides a valuable tool for isolating those subpopulations able to traverse basement membranes and to assess this capacity in new tumour samples.
Invasion Metastasis 1989
PMID:Selection of highly malignant tumour cells using reconstituted basement membrane matrix. 270 99

The successful penetration of endothelial basement membranes is an important process in the formation of hematogenous tumor metastases. Heparan sulfate (HS) proteoglycan is a major constituent of endothelial basement membranes, and we have found that HS-degradative activities of metastatic B16 melanoma sublines correlate with their lung-colonizing potentials. The melanoma HS-degrading enzyme is a unique endo-beta-D-glucuronidase (heparanase) that cleaves HS at specific intrachain sites and is detectable in a variety of cultured human malignant melanomas. The treatment of B16 melanoma cells with heparanase inhibitors that have few other biological activities, such as N-acetylated N-desulfated heparin, results in significant reductions in the numbers of experimental lung metastases in syngeneic mice, indicating that heparanase plays an important role in melanoma metastasis. HS-degrading endoglycosidases are not tumor-specific and have been found in several normal tissues and cells. There are at least three types of endo-beta-D-glucuronidases based on their substrate specificities. Melanoma heparanase, an Mr approximately 96,000 enzyme with specificity for beta-D-glucuronosyl-N-acetylglucosaminyl linkages in HS, is different from platelet and mastocytoma endoglucuronidases. Elevated levels of heparanase have been detected in sera from metastatic tumor-bearing animals and malignant melanoma patients, and a correlation exists between serum heparanase activity and extent of metastases. The results suggest that heparanase is potentially a useful marker for tumor metastasis.
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PMID:Heparanases and tumor metastasis. 328 60

To determine if the amount of chondroitin sulfate proteoglycan (CSPG) in human colorectal tumor tissue correlates with the tumor's aggressiveness we immunochemically determined the CSPG levels in colorectal carcinomas at different stages. A total of 50 specimens--4 polyps, 15 stage B tumors, 9 stage C tumors, 12 stage D tumors, 7 liver metastases, and 3 lymph node metastases--were examined. Tumor tissues were extracted with 4 M guanidine hydrochloride containing protease inhibitors. The extracts were serially diluted and blotted onto nitrocellulose membranes. Reactivity of a chondroitin sulfate-specific mouse monoclonal antibody (CS-56) was determined by biotinylated goat antimouse Ig and avidin-biotin-peroxidase complex. After comparing tissues from tumors at different stages (classified by the presence or absence of metastasis), we could not find a positive or negative correlation between the amount of CSPG in primary colorectal carcinoma tissues and the tumor's metastatic potential. However, the metastatic foci in the liver or lymph node contained higher amounts of CSPG than the primary tumors did. Immunohistochemical staining of colon carcinoma tissue with CS-56 revealed that CSPG is predominantly localized in fibrotic portions in the tumor tissues. Two-year follow-up studies indicated that a high level of CSPG in primary tumors was not predictive of recurrence.
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PMID:Increased content of chondroitin sulfate proteoglycan in human colorectal carcinoma metastases compared with the primary tumor as determined by an anti-chondroitin-sulfate monoclonal antibody. 328 48

There is a growing realization that the whole tumor cell-matrix complex must be investigated in order to fully understand the process of cancer growth and metastasis. Proteoglycans are intrinsic constituents of the cell surface, extracellular matrix, and basement membrane, three logistically and functionally important structures involved in most cellular interactions. Proteoglycans influence the behavior of normal and malignant cells by virtue of their expanded configuration, polyanionic nature and, most of all, by their ability to interact with a variety of cellular products. Consequently, they have been implicated in a number of biological processes including proliferation, recognition, adhesion, and migration. They can serve as links between the extracellular and intracellular environment and thus transduce key biological signals. They can act as receptors for interstitial collagens and other matrix proteins and thus contribute to the organization of pericellular matrix. During neoplastic development there is a profound structural rearrangement of these macromolecules at both the plasma membrane and the pericellular level. Qualitative and quantitative abnormalities in proteoglycan metabolism may contribute to the establishment of some well-known neoplastic properties, including lack of cohesiveness, abnormal assembly of extracellular matrix, abnormal growth, and invasion. The present work will focus on recent advances in our understanding of these complex macromolecules and on some of the alterations associated with the neoplastic phenotype, and will then attempt to elucidate some of the mechanisms regulating these changes.
Cancer Metastasis Rev 1988 Apr
PMID:Proteoglycans and neoplasia. 329 31


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