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 gingival localization of fibrosarcoma of soft oral tissues was described in a 58-year-old female. Primary fibrosarcoma of the head and neck region is rare. The histological appearance of the tumour is related to its grade of differentiation. The amount of collagen is variable. The accepted treatment is radical surgery; but metastases occur frequently in the lungs.
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PMID:Gingival localization of fibrosarcoma of soft oral tissues: case report. 144 89

The 72-kd type IV collagenase (matrix metalloproteinase-2 [MMP-2]) is a neutral metalloproteinase that initiates the degradation of type IV collagen in basement membranes. Its production by tumor cells has been correlated with the invasive and metastatic potential of neoplasms. Two recently developed affinity-purified antibodies against synthetic peptides from the amino terminus (H1) and an internal domain (Ab48) of the molecule were used to investigate immunohistochemically the distribution of this enzyme in a variety of thyroid tissues. All primary carcinomas (20 papillary, seven follicular, and three medullary) as well as nine of 11 metastases were positive, with the more aggressive tumors (tall cell variant of papillary carcinomas and invasive follicular carcinomas) tending to be more reactive than the low-grade tumors (classic and microinvasive papillary carcinomas and minimally invasive follicular tumors). Negative or minimal positivity was found in six cases of normal thyroid, one goiter, and two cases of Graves' disease. Immunoreactive follicular cells were seen focally in areas of inflammation, fibrosis, and distortion of normal follicles, and in Hashimoto's thyroiditis (four cases). Five of nine adenomas showed positive cells, but this could be related to previous trauma to the area. We conclude that there is increased production of the 72-kd type IV collagenase (MMP-2) in thyroid cancer; however, this enzyme also is elevated in benign conditions that are undergoing remodeling and repair.
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PMID:Distribution of the 72-kd type IV collagenase in nonneoplastic and neoplastic thyroid tissue. 146 77

A variant cell line (EL-4ad) which adhered to a tissue culture dish was isolated from highly metastatic EL-4 murine T-lymphoma. The experimental and spontaneous metastatic ability of EL-4ad was lower than that of the EL-4 parent cell line. The cell surface phenotypes of both cell lines were CD2+3+4-8-45+TCR alpha beta+TCR gamma delta-, but the level of CD2 expression of EL-4ad was much lower than that of EL-4. Furthermore, EL-4ad had higher binding ability to fibronectin and expressed more PNA receptors on the cell surface than EL-4. These differences indicated that either the maturation stage of the less metastatic variant was lower than that of the parent cell line or the activation state of the two cell lines differed. EL-4ad showed higher in vitro invasiveness and adhesiveness to liver cells, and these characters were not consistent with the reduced metastatic ability of this variant. Neuraminidase-releasable cell surface sialic acid levels did not differ significantly between the cell lines. Neither cell line was adhesive to laminin, type IV collagen or reconstituted basement membrane. These metastasis-related properties could not explain the decreased metastatic ability of EL-4ad. On the other hand, EL-4ad was more sensitive to NK activity than EL-4 in vivo, and this was thought to be a major cause of its decreased metastatic ability. The molecules or mechanisms involved in the differentiation or activation of T-cells may be responsible for the sensitivity of tumor cells to NK activity.
Clin Exp Metastasis 1992 Sep
PMID:Isolation and characterization of a low metastatic variant from EL-4 mouse T-lymphoma. 150 20

Cells contracting connective tissue matrices generate tractional forces in tissues. Studies of fibroblast contraction, using collagen gels in an in vitro model, demonstrate that it involves the actin cytoskeleton, specific extracellular matrix receptors and requires stimulation by exogenous promoters. Fibroblast contraction is stimulated by factors released by platelets and potentially secreted within the contracting tissue. Endothelial cells secrete a potent promoter of fibroblast contraction which has been identified as endothelin 1. The pathway through which fibroblast contraction is stimulated appears to require activation of protein kinase C. Tumor cells can also secrete endothelin. These mechanisms may be relevant to tumor progression.
Cancer Metastasis Rev 1992 Mar
PMID:Extracellular matrix contraction by fibroblasts: peptide promoters and second messengers. 151 96

Evidence has accumulated that invasion and metastasis in solid tumors require the action of tumor-associated proteases, which promote the dissolution of the surrounding tumor matrix and the basement membranes. Receptor-bound urokinase-type plasminogen activator (uPA) appears to play a key role in these events. uPA converts plasminogen into plasmin and thus mediates pericellular proteolysis during cell migration and tissue remodeling under physiological and pathophysiological conditions. uPA is secreted as an enzymatically inactive proenzyme (pro-uPA) by tumor cells and stroma cells. uPA exerts its proteolytic function on normal cells and tumor cells as an ectoenzyme after having bound to a high-affinity cell surface receptor. After binding, pro-uPA is activated by serine proteases (e.g. plasmin, trypsin or plasma kallikrein) and by the cysteine proteases cathepsin B or L, resp. Receptor-bound enzymatically active uPA converts plasminogen to plasmin which is bound to a different low-affinity receptor on tumor cells. Plasmin then degrades components of the tumor stroma (e.g. fibrin, fibronectin, proteoglycans, laminin) and may activate procollagenase type IV which degrades collagen type IV, a major part of the basement membrane. Hence receptor-bound uPA will promote plasminogen activation and thus the dissolution of the tumor matrix and the basement membrane which is a prerequisite for invasion and metastasis. Tissues of primary cancer and/or metastases of the breast, ovary, prostate, cervix uteri, bladder, lung and of the gastrointestinal tract contain elevated levels of uPA compared to benign tissues. In breast cancer uPA and PAI-1 antigen in tumor tissue extracts are independent prognostic factors for relapse-free and overall survival.
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PMID:Tumor-associated urokinase-type plasminogen activator: biological and clinical significance. 151 91

The presence of type IV collagen at the tumour/stromal interface of invasive carcinoma of the cervix was evaluated in 60 cases. It was assessed semi-quantitatively according to its staining characteristics, and expressed as: thick, with or without minimal discontinuity; thin, with or without moderate discontinuity; fragmentary or absent. In each case the tumour type was identified, the differentiation, growth pattern and peritumoural inflammatory infiltrate was graded and lymph node status established. There was, overall, a significant correlation between a paucity of type IV collagen and a poorer prognosis and an infiltrating growth pattern. There was a highly significant correlation for adenocarcinomas in relation to poor outcome, infiltrating growth pattern and lymph node metastases. By contrast, no statistically significant correlation was found between paucity of type IV collagen and the other parameters for either squamous or adenosquamous carcinomas. The presence of absence of type IV collagen may be a useful prognostic marker, particularly for adenocarcinomas, and may play a part in the invasive and metastatic process.
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PMID:The distribution of type IV collagen in invasive carcinoma of the uterine cervix. 155 68

The expression and distribution of the extracellular matrix (ECM) in 37 gliomas and 19 meningiomas were studied immunohistochemically by antibodies to type 3, 4 and 6 collagen, fibronectin and laminin. In gliomas the expression of these antigens was more intense and thicker in the tumor vessel walls, and was positively correlated to the malignant degree of the gliomas. This suggests that the thickening of the vessel walls and the increase of their ECM components in gliomas may be one of the causes why gliomas are extremely rare to metastasize to the outside of the cranium. All the above-cited ECM were positive in the fibroblastic type of meningioma, being just located between the tumor cells; whereas in syncytial type they were negative. This indicates that the immunohistochemistry of ECM may be of advantage in differentiating meningioma type.
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PMID:[Immunohistochemical study of extracellular matrices in human glioma and meningioma]. 164 41

A case is reported of Wilms' tumor associated with multiple pulmonary metastases histologically showing maturation of the tumor cells at 9 years after the resection of the primary tumor and intensive therapy. A huge tumor of a 22-month-old patient's right kidney was resected. The tumor was diagnosed as Wilms' tumor of mesenchymal type (stage 1), which consisted of predominantly immature mesenchymal tissue including rhabdomyoblasts, smooth muscle and fibrous tissue, and few blastemal and epithelial components. Intensive preoperative and postoperative chemotherapy with actinomycin D and vincristine and postoperative irradiation therapy totaling 16 Gy were carried out. The patient was regularly followed up uneventfully until 9 years after the surgery. On routine chest x ray at the age of 10 years 11 months, multiple pulmonary nodules were found. The excised nodules from the bilateral lungs disclosed similar histology, exclusively composed of dense collagen bundles and fibrocytes intermingled with mature striated muscle bundles. No immature tumor components were detected. The possible effect of intensive therapy in this maturation was stressed, although spontaneous benign differentiation of tumor cells cannot be excluded.
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PMID:Maturation of pulmonary metastases of Wilms' tumor after therapy: a case report. 165 May 75

Human prostatic acid phosphatase (hPAP) directly enhances the differentiated characteristics of isolated bone cells in vitro. This enzyme, when added to cell cultures for 24 h in vitro stimulates collagen synthesis and the production of alkaline phosphatase. The effects are dose dependent, with statistically significant effects occurring from 0.1-100 nM hPAP. Concentrations higher than 100 nM do not evoke greater effects. The maximal effect of hPAP occurs between 12 and 24 h of exposure. The cells stimulated to the greatest degree are osteoprogenitor cells and osteoblasts. Fibroblasts isolated from the same tissue show a lesser sensitivity to hPAP. hPAP has no detectable effect on cell proliferation, as measured by radiolabeled thymidine incorporation or total DNA synthesis. None of the observations reported in this work can be attributed to contaminating proteins in the hPAP preparation. hPAP was radiolabeled with 125I and was used for affinity binding and cross-linking studies. Scatchard analysis of specific binding indicated the presence of 1.0 X 10(5) high affinity binding sites/cell, with a Kd of 6.5 nM. Cross-linking studies demonstrated the presence of one 320-kDa binding complex. The pH profile and kinetic determinations of Km and maximum velocity for hPAP were similar to those previously reported, except for the finding of positive cooperativity of the substrate with the enzyme under the conditions of our assay. We believe that the direct stimulation of bone-forming cells by hPAP may contribute to the sclerotic nature of skeletal bone around sites of neoplastic prostatic metastases and that the effect of the enzyme is probably mediated by a plasma membrane receptor.
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PMID:Human prostatic acid phosphatase directly stimulates collagen synthesis and alkaline phosphatase content of isolated bone cells. 165 83

Functional characteristics of the interstitial collagenase purified from the BCl rat mammary carcinoma cell line were examined and compared with literature reports of the corresponding characteristics of collagenase from non-neoplastic cells. BCl collagenase degraded soluble collagen types I, II and III at the same rate and degraded fibrillar tendon collagen with an activation energy of 75 kcal/mol; these characteristics were identical to collagenase from normal rat uterine smooth muscle cells. Degradation of fibrillar collagen by BCl collagenase was completely inhibited by rat alpha 2-macroglobulin which was concomitantly cleaved into half-fragments. BCl collagenase was also inhibited by native and recombinant tissue inhibitor of metalloproteinases, a synthetic peptide collagenase inhibitor (Z-pro-leugly-NHOH), and Zn2+. In all functional characteristics examined, BCl collagenase was the same as interstitial collagenases from non-neoplastic sources.
Invasion Metastasis 1991
PMID:Interstitial collagenase from rat mammary carcinoma cells: interaction with substrates and inhibitors. 166 66


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