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)

In a previous work we found a correlation between in vivo metastatic potential of cancer cells and their platelet aggregating activity in sublines of the mFS6 murine fibrosarcoma. In the present study the effects of different proteinase inhibitors on platelet aggregation induced by these cells were investigated. When the platelets were incubated with the inhibitors, only those effective against cysteine proteinases strongly reduced platelet aggregation by cancer cells; serine protease inhibitors, including hirudin, had no effect on platelet response. Incubation of neoplastic cells with the same inhibitors gave similar, though less evident results. Addition of neoplastic cells to platelet-rich plasma also caused significant production of fibrinopeptide A, more by the less malignant cells. Thus, in this experimental model a cysteine proteinase of the neoplastic cells appears to play an important role in the platelet aggregation induced by them, and this property was detected in the M4 cells with high metastatic in vivo activity.
Invasion Metastasis 1986
PMID:Role of tumor proteinases in tumor cell-induced platelet aggregation. 353 93

Cysteine proteinases are a subclass of endopeptidases which require activation by thiol reagents. A tumor cysteine proteinase which appears to be related to lysosomal cathepsin B has been implicated in the ability of tumor cells to invade the extracellular matrix and to metastasize to secondary sites. Lysosomal cathepsin B can degrade such components of the extracellular matrix as collagen, fibronectin and proteoglycans. Activity of this cathepsin B-like cysteine proteinase (CB) has been correlated with tumor malignancy in a number of tumor lines yet not in all tumor lines studied. CB activity in tumors seems to be associated with the viable tumor cells, probably with the plasma membrane of these tumor cells. CB activity has been measured in the sera, urine, ascites fluid and pancreatic fluid of tumor-bearing patients. CB is released from tumor explants and tumor cells in vitro as well as from normal subcutaneous tissue exposed to tumor-conditioned medium. Cathepsin B from normal tissues is rapidly inactivated above pH 7.0. Therefore, CB in tumor cell membranes or released from tumor cells (or from host cells in response to tumor cells) may not possess proteolytic activity at neutral pH and thus may not facilitate tumor cell invasion. However, CB exhibits enhanced stability at neutral or slightly alkaline pH's. There is not yet definitive proof that CB plays a role in tumor invasion and metastasis. There is, however, an increasing body of correlative evidence relating CB activity and tumor malignancy. This correlative evidence plus preliminary evidence that tumor CB can degrade components of the extracellular matrix in vitro suggests that CB may be one proteinase active in a proteolytic cascade resulting in tumor invasion and metastasis.
Cancer Metastasis Rev 1984
PMID:Cysteine proteinases and metastasis. 609 95

Murine 15091A mammary adenocarcinoma cells and membrane vesicles spontaneously shed from these tumor cells in culture can induce aggregation of washed human platelets. A spectrum of proteinase inhibitors was tested for their ability to inhibit 15091A induced platelet aggregation. Of the inhibitors tested the most effective were those selective for cysteine proteinases. The effect of the spectrum of proteinase inhibitors on 15091A induced platelet aggregation was compared to the effect on cathepsin B-like cysteine proteinase activity in homogenates of 15091A tumor cells and their spontaneously shed vesicles. The results suggest that there is a correlation between activity of a cathepsin B-like proteinase in 15091A cells and vesicles and the ability of these cells and vesicles to induce aggregation of washed human platelets.
Clin Exp Metastasis
PMID:Involvement of a cathepsin B-like cysteine proteinase in platelet aggregation induced by tumor cells and their shed membrane vesicles. 640 Apr 36

The ability of tumor cells to metastasize may be related to their ability to promote aggregation of host platelets. The use of inhibitors of cysteine proteinases resulted in parallel inhibition of B16 amelanotic melanoma-induced platelet aggregation and of a cathepsin B activity. The antimetastatic agent prostacyclin inhibited platelet aggregation induced by the tumor cells and by papain, a cathepsin B-mimicking agent.
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PMID:Tumor cell-platelet aggregation: induced by cathepsin B-like proteinase and inhibited by prostacyclin. 704 53

CART1, a novel human gene, encodes a putative protein exhibiting three main structural domains: first, a cysteine-rich domain located at the amino-terminal part of the protein, which corresponds to an unusual RING finger motif; second, an original cysteine-rich domain located at the core of the protein and constituted by three repeats of an HC3HC3 consensus motif that we designated the CART motif, and which might interact with nucleic acid; third, the carboxyl-terminal part of the CART1 protein corresponds to a TRAF domain known to be involved in protein-protein interactions. Similar association of RING, CART, and TRAF domain was observed in the human CD40-binding protein and in the mouse tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2), both involved in signal transduction mediated by the TNF receptor family and in the developmentally regulated Dictyostelium discoideum DG17 protein. CART1 is specifically expressed by epithelial cells in breast carcinomas and metastases. Moreover, in these malignant cells, the CART1 protein is localized in the nucleus. Altogether, these observations indicate that CART1 may be involved in TNF-related cytokine signal transduction in breast carcinoma.
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PMID:Presence of a new conserved domain in CART1, a novel member of the tumor necrosis factor receptor-associated protein family, which is expressed in breast carcinoma. 759 51

Cathepsin B and cathepsin L--cysteine proteinases--may play an important role in cancer invasion and metastasis. The authors determined tissue antigen concentrations of cathepsins, using the ELISA method, in 25 patients with gastric cancer (17 males, 8 females, mean age 62, range 31-84). They evaluated the possible relationship that these proteinases may have with the presence of metastases, differentiation and histotype. Significantly higher cathepsin B and cathepsin L antigen levels were found: 1. in gastric cancer tissues vs. normal tissues distant from tumors (CATB: p < 0.05, CATL: p < 0.005); 2. in diffuse vs. intestinal type cancers (p < 0.05); 3. in patients with poorly vs. well-differentiated cancers (p < 0.05); in gastric cancers with vs. without metastasis (p < 0.05). Their results confirm that cathepsin B and L play an important role in gastric cancer invasion and metastasis. Considering the significantly higher cathepsins detected in cancers with metastasis, a poor differentiation and of diffuse histotype, these proteinases could be useful for identification gastric cancer patients with a poor prognosis.
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PMID:[Role and behavior of cathepsin B and cathepsin L in gastric cancer]. 759 89

The expression of three lysosomal cysteine proteases was examined in a lowly metastatic, MCF-7 human breast cancer cell line and its highly metastatic, Adriamycin-resistant variant, MCF-7/AdrR. While levels of cathepsin H activity were similar in all cell lines at each stage of growth, intracellular cathepsin B and L activities were highest in MCF-7/AdrR. These high levels were accompanied by growth-related increases in acid/pepsin-activatable cathepsin activity in the culture medium. Analyses of endogenous cathepsin B inhibitor activity in control and heat-treated cell homogenates after fractionation by fast protein liquid chromatography suggested that alterations in cystatin-like, cysteine protease inhibitor activities contribute to increased levels of cathepsin activities in metastatic MCF-7/AdrR cells.
Invasion Metastasis 1993
PMID:Characterization of cysteine proteases and their endogenous inhibitors in MCF-7 and adriamycin-resistant MCF-7 human breast cancer cells. 786 Feb 23

Malignant tumors derived from 60 patients with primary ovarian cancer were assayed for lysosomal cysteine proteinases--cathepsins B and L (Cat B, Cat L) and lysosomal aspartyl proteinase--cathepsin D (Cat D) as compared with benign ovarian tumors in controls. Malignant ovarian tumors exhibited significantly increased Cat B and Cat L activity (18.5- and 9-fold, respectively, p < 0.001) and moderately increased Cat D activity (1.5-fold, p < 0.01) as compared with those of benign tumors. The data obtained indicate that malignant ovarian tumors with a high Cat B activity (higher than the critical level of 723.5 +/- 100.0 Opmol/min. mg protein) proved to be more malignant in nature (low cell differentiated tumors predominated with early metastases spreading and relapses). Retrospective analysis of the disease development in 38 patients with ovarian tumors revealed that patients with early relapses (within the first year after surgery) demonstrated higher Cat B activity in tumors as compared with both the critical level and with that of patients without relapses; in the latter group the increase was found to be 2.4-fold (p < 0.01). The rate of CatB activity increases proved to be 56% and 8% in patients with and without relapses, respectively. Therefore, evaluation of the critical level of CatB activity in patients with primary ovarian cancer may be employed for prognostic purposes.
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PMID:[Prognostic significance of determining cathepsin B activity in malignant ovarian tumors]. 812 4

The human genome contains large regions that are highly structured. Sequence-related members of multigene families are often found in a clustered organization. Here we describe a previously unrecognized gene cluster composed of genes coding for calcium-binding proteins of the S100 family. The linkage of six S100 genes was established by pulsed-field gel electrophoresis, and a contiguous DNA sequence of 15 kilobases containing the full coding region of four different S100 genes was characterized. This is the tightest mammalian gene cluster discovered so far to our knowledge. Two additional S100 genes are located within the cluster, both of which exhibit unique structural features when compared with other S100 genes. The product of S100E is cysteine-rich, whereas that of S100D contains a long hydrophobic N-terminal tail. The gene cluster was assigned to chromosome 1q21, one of the bands showing rearrangements in neoplasms at high frequency. The deregulated expression of some S100 genes in the cluster during tumor progression suggests that chromosomal abnormalities may influence the expression of S100 genes in late stages of cancer, particularly in association with the formation of metastases.
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PMID:Six S100 genes are clustered on human chromosome 1q21: identification of two genes coding for the two previously unreported calcium-binding proteins S100D and S100E. 834 67

Increased levels of human cysteine proteases have been implicated in the progression of tumors from the premalignant to the malignant state. The physiological activities of these proteases are regulated by their interactions with specific inhibitors. To our knowledge there have been no previous reports about the cysteine protease inhibitors (CPIs) in human brain tumors. In the study reported here, we determined CPI activity during glioma progression and compared that with normal human brain tissue. We also determined CPI activities in meningioma and glioblastoma cell lines in vitro. This activity was significantly higher in normal brain tissue and low-grade glioma than in anaplastic astrocytoma and glioblastoma. CPI activity was significantly higher in benign and atypical meningioma cell extracts in comparison with those from malignant meningiomas and with those from glioblastoma cell lines. After several passages, one benign meningioma cell line showed reduced levels of CPI and increased levels of cathepsin. Our results suggest that decreases in the activities of CPI may contribute to the malignant properties of brain tumors.
Clin Exp Metastasis 1996 Sep
PMID:Expression of cysteine protease inhibitors in human gliomas and meningiomas. 887 8


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