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)

Epithelial cell lines (BC1, BC3, BC4, and BC5), derived from 4 separate invasive and metastatic rat mammary carcinomas, all secreted interstitial collagenase (matrix metalloproteinase 1, MMP 1) in culture. Neither a cloned cell line (A5P/B10), derived from a noninvasive rat epithelial tumor, nor nonneoplastic rat fibroblasts secreted the enzyme. Western blot analyses of proteins extracted from the plasma membranes indicated the presence of interstitial collagenase (MMP 1) on the surface of all of the 6 cell lines. These data suggest that the control of collagenolysis may involve the association of collagenase molecules with the plasma membrane. The aggressiveness of malignant tumors may be due in part to the breakdown of such a control.
Invasion Metastasis 1991
PMID:Interstitial collagenase (matrix metalloproteinase 1) associated with the plasma membrane of both neoplastic and nonneoplastic cells. 165 15

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

Implantation and subsequent placental development in many species including the human are dependent on trophoblast invasion of the uterine epithelium, the underlying basement membrane, connective tissue and blood vessels. However, trophoblast invasion in situ is strictly controlled by the microenvironment provided by the pregnant uterus. Key mechanisms underlying various steps in trophoblast invasion of basement membrane and stroma are similar to those identified in the case of invasive tumor cells: (a) attachment to basement membrane by binding to laminin and possibly other basement membrane components; (b) detachment from the basement membrane matrix prior to its penetration, a process that requires the presence of complex-type oligosaccharides on the cell surface; (c) breakdown of basement membrane components by trophoblast-derived metalloproteases (type IV and interstitial collagenase) and serine proteases (plasminogen activator). Type IV collagenase activity is stimulated by binding to laminin, a molecule also secreted by the trophoblast. Activation of trophoblast-derived metalloproteases appears to be plasmin-dependent. Plasmin results from the cleavage of plasminogen by trophoblast-derived plasminogen activator. Control of trophoblast invasion in situ is mediated by decidua-derived transforming growth factor beta (TGF beta) which in turn induces tissue inhibitor of metalloproteases (TIMP) both in the decidua and the trophoblast. We suggest that this control of trophoblast invasiveness is regulated both spatially as well as temporally during gestation. A preprogrammed decline in trophoblast invasiveness with increasing gestational age remains an additional possibility. The nature of the loss of control of trophoblast invasiveness in choriocarcinoma remains to be identified. Refractoriness to TGF beta action remains to strong possibility.
Cancer Metastasis Rev 1990 Dec
PMID:Mechanisms of trophoblast invasiveness and their control: the role of proteases and protease inhibitors. 209 85

In order to investigate the role of collagenase in cancer invasion and metastasis, two collagenase activities of interstitial collagenase and type IV collagen degrading enzyme (type IV collagenase) were determined in 40 cases of human stomach cancer tissue. Elevated cancers which are known to have a propensity to cause blood-borne metastases showed higher activities of both interstitial collagenase and type IV collagenase than flat or ulcerous type of cancer. Using the parameters of lymph node metastasis vs tumor size or vs depth of cancerous invasion into the stomach wall, classification of the cases was attempted according to the degree of malignancy. In the cases with marked lymph node metastases in spite of small tumor size and/or shallow cancerous invasion into the stomach wall, type IV collagenase activity was higher than that in the cases with lower malignancy (p less than 0.025, p less than 0.05, respectively). These results suggest that collagenase in stomach cancer tissue play an important role in the invasion and metastasis of cancer cells. Type IV collagenase activity in stomach cancer tissue could be one of the useful biological markers for the degree of malignancy.
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PMID:The collagenase activities, interstitial collagenase and type IV collagenase, in human stomach cancer: with special reference to local spreading and lymph node metastasis. 217 1

In this review the production of interstitial collagenase in DMBA-induced mammary tumors of the rat has been examined. Cell sorting and cell cultures have given us the opportunity to relate the release of collagenase to a specific cell type. By means of FITC-fluorescence and monospecific antibodies (S. Sakamoto, Harvard University, Boston) it was further possible to localize collagenase in vitro and in vivo. The most outstanding characteristic is that collagenase is produced both by cuboidal, epithelial cell and by macrophages in vitro but not by myoepithelial-like cells. On the other hand, synthesis of collagenase in vivo was detected in some stromal cells, possibly macrophages, but not in neoplastic cuboidal cells. This observation has been related to the inability of cuboidal cells to interact with stromal, fibrillar collagen in vivo since tumor cells are arranged in glandular-like structures bordered by myoepithelial cells and a basement membrane. In vitro, fibrillar rat tail tendon collagen was found to be a potent stimulator of collagenase production by cuboidal cells. Collagenase stimulation by interstitial collagen therefore suggests a plausible mechanism for the degradation of collagen fibrils during local invasion by mammary tumor cells.
Cancer Metastasis Rev 1984
PMID:Biological significance of interstitial collagenase in DMBA-induced mammary tumors of the rat. 609 94

Loss of negative growth regulation and high invasive potential are neoplastic traits often associated with abnormal expression of matrix metalloproteinases (MMPs). We previously found MMP-3 (stromelysin/transin) was secreted by quiescent rat Schwann cell cultures and expressed potent antiproliferative activity. In the present study we observed that human Schwann cells and cutaneous neurofibroma Schwann cell cultures secreted abundant MMP-3 and their proliferation was inhibited by autologous and rat Schwann cell conditioned media. Antiproliferative activities were depleted by immunoadsorption with anti-stromelysin antibodies. In contrast, plexiform neurofibroma cultures did not secrete MMP-3 and failed to respond to Schwann cell antiproliferative activities associated with MMP-3. Quiescent Schwann cells constitutively secreted low levels of MMP-2 (gelatinase A) and showed a low invasion potential in filter-based assays of basement membrane invasion. Cyclic AMP elevation, which profoundly influences cell differentiation, increased the invasion potential of rat Schwann cells and caused a corresponding increase in secretion of MMP-2. Schwann cells immortalized by protracted elevation of cAMP, as well as a schwannoma cell line (D6P2T), also rapidly invaded a reconstituted basement membrane and over-expressed MMP-2. Similarly, neurofibroma Schwann cells were highly invasive and secreted up to 10-fold more MMP-2 than normal human Schwann cells. Additionally, only cutaneous neurofibroma Schwann cell cultures secreted MMP-9 (gelatinase B) and MMP-1 (interstitial collagenase) and also invaded native type I collagen barriers. Cultures of normal Schwann cells and plexiform neurofibroma tumor expressed little or no MMP-1 and did not invade type I collagen barriers. These results suggest a role for MMPs in the control of proliferation and invasion by Schwann cells and in the formation of peripheral nerve sheath tumors.
Clin Exp Metastasis 1995 Jul
PMID:Differences in proliferation and invasion by normal, transformed and NF1 Schwann cell cultures are influenced by matrix metalloproteinase expression. 760 93

Death from cancer results from the development of metastases or local progression of tumour. Metastasis and local progression may result from the inappropriate activity of metalloproteinases released by tumour cells or of their regulatory peptides. We have developed quantitative assays for interstitial collagenase, stromelysin 1 and tissue inhibitors of metalloproteinase (TIMP) 1 and 2, which have allowed the study of serum levels of these proteins. Sera from 40 patients with prostatic cancer, stored prior to and after 6 and 12 months' treatment with a gonadotrophin-releasing hormone agonist and an anti-androgen were analysed. Levels were compared with two control groups, comprising 21 patients with active rheumatoid arthritis and 56 age-matched hospital attenders without arthritis or cancer. Contrasting levels have been found in patients with prostatic cancer as compared with hospital controls without cancer and patients with rheumatoid arthritis. Patients with prostatic cancer had higher levels of TIMP-1 and collagenase (P = 0.0001) and lower levels of TIMP-2 (P = 0.003) than controls. Patients with metastatic cancer had significantly higher levels of collagenase than those without metastases (P = 0.02). Patients with rheumatoid arthritis had significantly higher levels of stromelysin than either controls (P = 0.002) or patients with cancer (P = 0.008). Serum tissue inhibitor of metalloproteinase 1 in combination with collagenase levels was as sensitive as prostate-specific antigen as a marker of metastatic disease. These findings provide a basis for the investigation of the role of metalloproteinases and their inhibitors in other malignancies.
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PMID:Serum metalloproteinases and their inhibitors: markers for malignant potential. 808 Jul 38

Matrix metalloproteinases (MMPs) are a group of enzymes thought to be responsible for both normal connective-tissue-matrix remodelling and the accelerated breakdown associated with tumor development. These MMPs and tissue inhibitor of MMPs (TIMP1) could be expressed by either the cancer or the stromal cells. Expression of mRNAs encoding interstitial collagenase (MMP1), 72-kD type IV collagenase (MMP2) and stromelysin (MMP3), which are probably involved in tumor invasion and metastasis, and of TIMP1 were studied in human mammary pathology by in situ hybridization and Northern blot analysis. Out of 6 benign lesions, 2 expressed MMP2 mRNAs. mRNAs encoding MMP1 and MMP3 were detectable in occasional stromal and tumor cells in 2 out of 17 carcinomas. Thirteen out of 17 cancers expressed MMP2 mRNA throughout the tumor in stromal cells close to noninvasive tumor clusters and well-differentiated invasive cancer cells. TIMP1 mRNA expression was detected in noninvasive and well-differentiated invasive tumor cells. These data suggest that there is a cooperation between tumor and stromal cells, in particular for the production of 72-kD type IV collagenase, involved in the disruption of basement membranes. A lack of TIMP1 expression from invasive cancer cells would also contribute to matrix destruction.
Invasion Metastasis 1993
PMID:Detection and localization of mRNAs encoding matrix metalloproteinases and their tissue inhibitor in human breast pathology. 840 9

Members of the metalloproteinase family (MMPs) are known to play a crucial role in the metastatic cascade. Here, we report some investigations about the synthesis of interstitial and type-IV collagenases (gelatinases A and B) in a model of coculture of human fibroblasts and HT 1080 fibrosarcoma cells. The interstitial collagenase activity, mainly found in the conditioned medium of fibroblasts, and its mRNA level were increased in the in vitro coculture model. In contrast, gelatinase A was produced by both cell types. The HT 1080 cells additionally synthesised gelatinase B. In coculture, an enhancement of gelatinase A and the presence of its activated form were observed. Northern blot analysis demonstrated that this enzymatic enhancement occurred at a pretranslational level. The stimulation of the interstitial collagenase activity was partially mediated through soluble factor(s), whereas increased gelatinase A appeared to require direct cell-cell interactions. The extracellular matrix component, type-I collagen, stimulated the enzymatic activities released by the individual cells, but it did not modulate the synthesis of interstitial collagenase in coculture. Our results demonstrate that distinct MMPs are modulated by distinct mechanisms, all depending on specific interactions between tumour cells and host fibroblasts.
Invasion Metastasis 1995
PMID:Modulation of the expression of interstitial and type-IV collagenases in coculture of HT1080 fibrosarcoma cells and fibroblasts. 876 91

The aim of the study was to assess the activities of the collagenases type IV (matrix metalloproteinase type 2 [MMP-2] and matrix metalloproteinase type 9 [MMP-9]), also known as gelatinases, and the local activity of interstitial collagenase (matrix metalloproteinase type I[MMP-1]) in tissue extracts from a case of the botryoid sarcoma, a rare and very malignant tumour of the female genital tract. Zymography revealed that botryoid sarcoma does not express the 92-kDa form of type IV collagenase activity in Triton extract and only weak activity in Heat extract when compared to values found in extracts from striated muscle and fibroma uteri. MMP-1 appeared in the latent form only in the Triton extract of botryoid sarcoma and its activity was lower than those found in the control tissues. These results indicate that the very rapid local invasion and systemic metastases associated with botryoid sarcoma do not depend on the activity of tumour-derived gelatinases.
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PMID:Local activity of matrix metalloproteinases in a case of botryoid sarcoma. 884 7


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