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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metalloproteases are implicated in conferring invasive properties to tumor cells. We show here that treatment of ras-oncogene-transformed rat fibroblasts with dimethylsulfoxide (DMSO) results in a reversible decrease in stromelysin mRNA. Furthermore, stromelysin expression was found to be repressed by DMSO, but not by glucocorticoid hormone, in a fibrosarcoma cell line showing low AP-1 (fos/jun) transcription factor activity. In two fibrosarcoma cell lines which express high levels of stromelysin and low levels of 68 kDa type IV collagenase, the DMSO-induced decrease in stromelysin expression was paralleled by a decreased invasive propensity.
Clin Exp Metastasis 1993 Jan
PMID:Repression of stromelysin metalloprotease expression in rat fibrosarcoma cells by dimethylsulfoxide. 842 9

The expression of both 92- and 72-kDa gelatinases has been studied in 20 samples of human breast carcinoma by the technique of gelatin zymography. This technique allowed the relative amount of each gelatinase to be determined in small samples of tissue (< 10 mg). More importantly, active and latent forms of the two gelatinases were resolved. Two samples (10-20 mg) were cut from each piece of tumour in order to monitor the variability of gelatinase distribution within that section of tumour. The 72-kDa latent progelatinase was present in 15 of the 20 tumours, with trace amounts in two others. The 62-kDa activated form of this gelatinase was detected in all 15 of the tumours in which the latent form was present. The 92-kDa latent progelatinase was present in 11 of the 20 tumours, with trace amounts in four others. However, the 82-kDa activated form of this gelatinase was only clearly detected in two tumours, although three others showed the presence of trace amounts. The ratio of active to latent forms of the 72-kDa gelatinase ranged from 0.9 to 3.6. There were no marked correlations between gelatinase expression and established staging and prognostic markers. Analysis of three samples of fibroadenoma revealed only very low levels of gelatinase expression. On the basis of these results, activation of the 72-kDa progelatinase appears to be a more common event in invasive breast carcinoma than activation of the 92-kDa progelatinase. However, neither proteinase showed a correlation with metastatic progression, as measured by lymph node involvement.
Clin Exp Metastasis 1993 Mar
PMID:Expression of activated gelatinase in human invasive breast carcinoma. 844 10

The expression of the stromelysin 3 (ST3) gene, which encodes a putative matrix metalloproteinase, was studied during breast cancer progression. The ST3 gene is expressed in all invasive breast carcinomas, in a number of their metastases, and in some in situ carcinomas where the probability of detecting ST3 transcripts correlates with the known risk of these carcinomas to become invasive. ST3 RNA and protein were specifically detected in fibroblastic cells immediately surrounding the neoplastic cells in both primary and metastatic tumors. This expression pattern distinguishes the ST3 gene from other matrix metalloproteinase genes, most notably from the 72-kDa type IV collagenase gene, which can be expressed in fibroblastic cells distributed throughout the stroma of primary breast carcinomas. Furthermore, high levels of 72-kDa type IV collagenase, but not of ST3 transcripts, are detected in benign breast fibroadenomas. Interestingly, the urokinase and ST3 genes exhibit very similar patterns of expression in breast carcinomas, which suggests that their products may cooperate during cancer progression.
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PMID:Stromelysin 3 belongs to a subgroup of proteinases expressed in breast carcinoma fibroblastic cells and possibly implicated in tumor progression. 844 98

Motility factors play a major role in tumor cell invasion and metastases. The biochemical properties of various motility factors; the receptor mediated mechanism of action; the role of microtubules; the potential influence of oncogenes; and the influence of motility factors on type IV collagenase secretion and invasion are discussed. We report on expression of a 70 kDa motility factor, termed invasion stimulating factor (ISF), in human prostatic PC-3 sublines. Boyden chamber chemotactic assays and measurements of type IV collagenase synthesis and secretion suggest that an ISF-receptor dependent mechanism influences tumor cell invasion and protease secretion. Taken together, the evidence that autocrine motility factors play an essential role in tumor cell invasion and metastases is compelling.
Cancer Metastasis Rev 1993 Mar
PMID:Autocrine factors, type IV collagenase secretion and prostatic cancer cell invasion. 844 26

We have previously shown that a 78-kDa "invasion stimulating factor" (ISF) triggers collagenase IV (MMP-2) secretion and the invasive behavior of metastatic PC-3 ML subclones in modified Boyden chamber assays [Stearns, M. E.; Stearns, M. Autocrine factors, type IV collagenase secretion and prostatic cancer cell invasion. Cancer Metastasis Rev. 12:39-52; 1993. Wang, M.; Stearns, M.; Stearns, M. E. Identification of the receptor for a novel M(r) 78,000 "invasion stimulating factor" from metastatic human prostatic PC-3 ML clones. Cancer Res. 54:2492-2495; 1994.]. Recently, we have shown that interleukin 10 (IL-10) preferentially stimulates tissue inhibitor of metalloproteinase-1 (TIMP-1) production in these cells [Wang, M.; Stearns, M. E. Characterization of a novel TIMP-1 enhancer element. J. Biol. Chem., submitted.]. In this paper, we report that IL-10 (20-40 ng) can inhibit the invasion stimulatory effects of ISF (30-60 ng) on PC-3 ML cells. "Checkerboard analysis" with modified Boyden chambers (precoated with 10 and 100 micrograms collagen IV) shows that IL-10 inhibits the stimulatory effects of ISF on both cell motility and chemoinvasion processes. In support of these data, exogenously supplied TIMP-1 (10 micrograms/ml) and collagenase antibodies (1:200 dilution) both completely blocked invasion. Quantitative ELISAs comparing the molar ratios of TIMP-1:MMP-2 and TIMP-2:MMP-2 further demonstrate that IL-10 (10-40 ng) preferentially activates TIMP-1 secretion to increase the molar ratio of TIMP-1:MMP-2 in the presence of increasing amounts of ISF (0-60 ng). IL-10 did not elevate TIMP-2 secretion or influence the molar ratio of TIMP-2:MMP-2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:IL-10 blocks collagen IV invasion by "invasion stimulating factor" activated PC-3 ML cells: upregulation of TIMP-1 expression. 855 49

MMP-2 (gelatinase A) has been associated with the invasive potential of many cancer cells both in vitro and in vivo. It is now becoming clear that the activation of this enzyme might be a key step in tumor invasion. This activation process has been shown to be a membrane-associated pathway inducible by various agents such as collagen type I, concanavalin A or TGF-beta, but its physiological regulation is still largely unresolved. MT-MMP was recently discovered and described as a potential gelatinase-A activator. In the present study, we investigated the expression of MT-MMP (membrane-type metalloproteinase) in cervical cancer cells both in vitro and in vivo. Comparing several in vitro-transformed cervical cell lines, previously shown to display different invasive potentials, our results showed that the ability of cells to overexpress MT-MMP mRNA following ConA induction correlated with their ability to activate gelatinase A and with a highly invasive behavior. Moreover, using immunohistochemistry and in situ hybridization, we found a higher level of MT-MMP expression in invasive cervical carcinoma and lymph node metastases compared to its expression in non-invasive CIN III lesions. Our in vivo observations also clearly demonstrated a cooperation between stromal and tumor cells for the production of MT-MMP. Taken together, our results clearly correlated high level MT-MMP expression with invasiveness, and thus suggested that MT-MMP might play a crucial role in cervical tumor invasion.
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PMID:High level of MT-MMP expression is associated with invasiveness of cervical cancer cells. 856 19

Human giant cell tumor (GCT) consists of multinucleated giant cells and mononuclear stromal cells, and is characterized by frequent vascular invasion without distant metastases. To study the role of matrix metalloproteinases (MMPs) in the vascular invasion, we examined production of MMP-1 (tissue collagenase), -2 (gelatinase A), -3 (stromelysin-1), -9 (gelatinase B), and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in GCT. MMP-9 was highly and predominantly expressed in giant cells by both immunohistochemistry and in situ hybridization. Expression of other MMPs was also observed in some cases but was inconstant. Sandwich enzyme immunoassays demonstrated that MMP-9 is the predominant MMP secreted by GCT. There was a definite imbalance between the amounts of MMP-9 and those of TIMPs in the culture media of GCT, leading to detectable gelatinolytic activity in an assay using 14C-gelatin. Gelatin zymography demonstrated the main activity at about 90 kd, which was identified as the zymogen of MMP-9 by immunoblotting. Immunohistochemistry for type IV collagen and laminin, major basement membrane components, showed that disappearance of the proteins is closely associated with MMP-9-positive giant cells. These results indicate the production of MMP-9 by multinucleated giant cells and suggest that the metalloproteinase may contribute to proteolysis associated with vascular invasion and local bone resorption in human GCT.
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PMID:Matrix metalloproteinase 9 (gelatinase B) is expressed in multinucleated giant cells of human giant cell tumor of bone and is associated with vascular invasion. 857 23

Diets rich in linoleic acid (LA) stimulate the metastasis of MDA-MB-435 human breast cancer cells from the mammary fat pads of nude mice. This omega-6 fatty acid is metabolized to various cyclo-oxygenase and lipoxygenase products, several of which have been previously associated with tumor cell invasion and metastasis. We now report that MDA-MB-435 cells secreted increased levels of prostaglandin E2 (PGE2), and 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-HETE when cultured in the presence of 2.7 microM (0.75 micrograms/ml) LA; 5-HETE secretion was unchanged. The 12-lipoxygenase inhibitor esculetin (20 microM) completely blocked the LA-stimulated 12-HETE secretion. Linoleic acid also increased MDA-MB-435 cell invasion in an in vitro assay; this stimulation was abolished by 20 microM esculetin, but was unaffected by piroxicam, a selective cyclooxygenase inhibitor. The effect of LA on invasion was replicated by 0.1 microM 12-HETE, but not by 5-HETE or PGE2; 15-HETE was stimulatory only at a concentration of 1.0 microM. Zymographic and Northern blot analyses showed that these events are accompanied by the induction of 92 kDa isoform type IV collagenase (metalloproteinase-9) enzymic activity and mRNA expression by exogenous LA and 12-HETE, and their suppression by the 12-lipoxygenase inhibitor. These results suggest that the effects of dietary LA on breast cancer cell metastasis in the nude mouse model are due, at least in part, to enhanced 12-HETE biosynthesis, with an associated increase in proteolytic enzyme activity and tumor cell invasiveness.
Clin Exp Metastasis 1996 Mar
PMID:Eicosanoids as mediators of linoleic acid-stimulated invasion and type IV collagenase production by a metastatic human breast cancer cell line. 860 28

To clarify the role of basic fibroblast growth factor (FGF-2) in the malignant progression of renal cell carcinoma, we transfected the FGF-2 gene, which lacks the typical signal sequence, into RenCa, a mouse renal cell carcinoma cell line that does not express FGF-2 mRNA. In an in vitro tumor cell invasion assay, the FGF-2-transfected cell lines (RenCa/F) exhibited 3- to 4-fold higher invasive potential than either the parental RenCa (RenCa/P) or the vector-only transfected cell line (RenCa/C). Zymography showed a marked increase in matrix metalloproteinase 2 (MMP-2) production in the culture supernatants of RenCa/F. Furthermore, when injected i.v. or into the renal subcapsule in syngeneic mice, RenCa/F formed more than 10 times as many metastatic nodules in the lung as did RenCa/P and RenCa/C. Metastases to the liver and mesenteric lymph nodes were observed only after the injection of RenCa/F into the renal subcapsule. In contrast, there was no significant difference in either cell proliferation in vitro or tumor growth in vivo among RenCa sublines. These results suggest that if it is overexpressed, endogenous native FGF-2 plays an important role in the invasion and metastasis of renal cell carcinoma, probably through the production of MMP-2.
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PMID:Introduction of basic fibroblast growth factor gene into mouse renal cell carcinoma cell line enhances its metastatic potential. 862 25

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


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