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At least 901 records · Page 50Linked to original sources
PubMed2005

Plasminogen activator inhibitor type 1 promotes fibrosarcoma cell migration by modifying cellular attachment to vitronectin via alpha(v)beta(5) integrin.

Both urokinase plasminogen activator (u-PA) and plasminogen activator inhibitor type 1 (PAI-1) are associated with a poor prognosis in cancer patients. We demonstrate that PAI-1 inhibits human fibrosarcoma cell (HT-1080) adhesion to vitronectin (Vn) via alpha (v)beta (5) integrin, and stimulates cell migration from Vn toward collagen type IV (Col). The cells attached more strongly to Vn and Col than to fibronectin (Fn), whereas PAI-1 interfered with cell attachment to Vn only. An integrin antagonist, RGD peptide, and anti-alpha (v)beta (5) integrin antibodies, which similarly inhibited cell attachment to Vn, also stimulated cell migration from Vn toward Col. u-PA did not modify cell attachment directly, but reversed the PAI-1-mediated inhibitory effect on cell adhesion to Vn, and its stimulatory effect on cell migration from Vn toward Col. Thus HT-1080 cell migration appears to be modified by u-PA and PAI-1, altering cell adhesion to Vn via alpha (v)beta (5) integrin. This may be related to their tumor-promoting effect.

Cell Adhesion↗
PubMed1998

Inhibitory effect of delphinidin from Solanum melongena on human fibrosarcoma HT-1080 invasiveness in vitro.

We investigated the inhibitory effect of eggplant (Solanum melongena var. marunasu) extract on human fibrosarcoma HT-1080 cell invasion of reconstituted basement membrane [Matrigel (MG)]. We found that the effective component of the plant extract was delphinidin, a flavonoid pigment contained in the peel. The extract and delphinidin did not affect tumor cell adhesion to MG or haptotactic migration to MG. HT-1080 secretes matrix metalloproteinase(MMP)-2 and MMP-9, which degrade extracellular matrix as part of the invasive process. Delphinidin slightly inhibited the activity of MMPs, which may have been responsible, in part, for the inhibition of tumor cell invasiveness.

Anthocyanins↗
PubMed1985

Stimulatory effect of epidermal growth factor on prostaglandin E2 production in mouse fibrosarcoma cell line (HSDM1 C1).

Using HSDM1 C1 cell line derived from the mouse fibrosarcoma which synthesizes and secretes prostaglandin (PG) E2, specific binding sites for epidermal growth factor (EGF), a potent growth stimulator of many tissues, and its effect on PGE2 production by cultured tumor cells were studied. HSDM1 C1 cell line possessed specific, high-affinity receptors for EGF: Kd (5.5 X 10(-10 M) and binding capacity (17,650 sites/cell). EGF significantly stimulated PGE2 production in HSDM1 C1 line cultured in serum-free medium for 24 h in a dose-dependent manner; a 2.5-fold increase over control was induced by as little as 0.1 ng/ml and the maximal effect (3.5-fold increase) by 1 ng/ml. Its stimulatory effect on PGE2 production was completely blocked by indomethacin, an inhibitor of PG biosynthesis. These data suggest that EGF may be involved in modulation of synthesis and/or secretion of PGE2, a potent bone-resorbing factor, by the tumors which may partly contribute to hypercalcemia in certain types of neoplasms.

Animals↗
PubMed1992

Intracardiac primary fibrosarcoma. Case report and literature review.

A 58-year-old woman was hospitalized because of shortness of breath, cough, weakness, and physical signs suggestive of mitral stenosis. Echo-Doppler examination revealed a left atrial mass. This was removed and turned out to be a fibrosarcoma. Recurrence of the tumor with metastases into the pericardium, thyroid goiter, and left kidney led to the patient's death 6 months later. The clinical and pathological features of our rare case are compared with those in the literature.

Female↗
PubMed1995

[Spontaneous malignant transformation of extra-abdominal fibromatosis to fibrosarcoma].

The desmoid tumour with infiltrative and destructive growth tendencies, is a rare benign alteration of the connective tissue from musculo-aponeurotic structures and fascial sheaths. The exact pathogenesis is unknown, however trauma (surgery), genetic (Gardener's Syndrome) or hormonal factors (pregnancy) have been implicated. A spontaneous malignant transformation of a desmoid (extra-abdominal fibromatosis) to a fibrosarcoma is a rarity. Only one case is recorded in the literature. We report on the second case in international literature and describe the coherence to an endocrine factor (pregnancy), the high recurrence rate and the difficulty of therapy with regard to the risk of late malignant transformation.

Adult↗
PubMedDate not supplied

[Surgical amputation and prosthetic management in congenital fibrosarcoma of the lower extremity].

The concept of surgical amputation and the problems of prosthetic management in a girl with congenital fibrosarcoma of left distal thigh, knee and shank is described. After failed polychemotherapy (EICESS 92) and expansion of the tumor a radical knee disarticulation and intended marginal resection of the tumorous soft tissue area of the distal thigh was performed at the age of eleven months and two weeks. The femur was shortened by osteotomy of the diaphysis and removing a fragment in order to protect the distal femoral epiphyseal growth plate and to be able to close the soft tissue of the stump primarily. Prosthetic fitting and rehabilitation started at the beginning of statomotorical development at the point when four feet standing changed into two feet standing. In present, at the age of two years and six months, this girl is independent mobile and well fitted with a knee disarticulation prosthesis.

Amputation, Surgical↗
PubMed2003

Loss of p16INK4a results in increased glucocorticoid receptor activity during fibrosarcoma development.

Glucocorticoids inhibit proliferation of many cell types, but the relationship between the glucocorticoid receptor (GR) and the proteins regulating cell cycle progression is not fully understood. We previously found that during fibrosarcoma (FS) progression, GR displays only modest transcriptional activity in the preneoplastic stages, whereas it is highly active in FS cells. Now, we report that glucocorticoids reduce proliferation throughout FS development. The cyclin-dependent kinase inhibitor p16(INK4a) is frequently absent in many cancers, including FSs. We observed that p16(INK4a) protein expression is lost at the tumor stage of FS progression. Treatment with the demethylating agent 5-aza-2'-deoxycytidine restores p16(INK4a) expression and reverts the phenotype of FS cells to low GR transcriptional activity, similar to that of the p16(INK4a)-expressing preneoplastic stages. Importantly, exogenous p16(INK4a) introduced by cotransfection is sufficient to reduce GR activity in FS cells, without affecting GR activity in p16-positive aggressive fibromatosis cells. Furthermore, GR transcriptional activity is elevated in mouse embryo fibroblasts derived from INK4a(-/-) mice compared with those derived from WT mice, implying that the difference in p16(INK4a) expression is sufficient to modulate GR activity. These results suggest a relationship between steroid hormone receptor activity and cell cycle inhibition, whereby absence of p16(INK4a) protein leads to higher GR transactivation activity and reduced cell sensitivity to dexamethasone. This observation might have important implications for current cancer therapies.

Animals↗
PubMed1976

Loss of mouse chromosomes in somatic cell hybrids between HT-1080 human fibrosarcoma cells and mouse peritioneal macrophages.

Somatic cell hybrids between mouse peritioneal macrophages and HT-1080 human fibrosarcoma cells lose mouse chromosomes and retain the entire complement of human chromosomes. In contrast, somatic cell hybrids between cells derived from two different mouse continuous cell lines and HT-1080 human cells were found to lose human chromosomes preferentially. Loss of mouse chromosomes is not a general property of hybrids between mouse macrophages and transformed human cells; the hybridization of mouse macrophages with cells derived from five different human fibroblast lines transformed by simian virus 40 resulted in the production of hybrid clones that preferentially lost human chromosomes.

Animals↗
PubMed1985

Synthesis and secretion of proteins resembling platelet-derived growth factor by human glioblastoma and fibrosarcoma cells in culture.

Immunoprecipitation of proteins extracted from metabolically labeled human glioblastoma and fibrosarcoma cells with antiserum to platelet-derived growth factor (PDGF) showed that these cells express and secrete proteins that are recognized specifically by the antiserum. The molecular masses of immunoprecipitated proteins in the lysates of the malignant cells ranged from 16 kDa to 140 kDa. Both cell lines secreted a 31-kDa polypeptide with structural, immunological, and biological properties similar to those of human PDGF. These cell lines were shown to synthesize a 4.4-kb mRNA that contained sequences from all the six currently identified exons of the human c-sis gene. These data suggest that the PDGF-like proteins in the two mesenchyme-derived transformed cells are encoded at least in part by the c-sis locus.

Cell Line↗
PubMed1990

Plasminogen-activator inhibitor type 1 is a potent natural inhibitor of extracellular matrix degradation by fibrosarcoma and colon carcinoma cells.

We have analyzed the role of plasminogen-activator inhibitor type 1 (PAI-1) in the regulation of tumor cell-mediated extracellular matrix degradation. Immunocytochemical analysis revealed PAI-1 associated with microgranular and fibrillar material of the extracellular matrix and demonstrated the presence of PAI-1 as a cell surface-associated antigen. Transforming growth factor beta significantly reduced matrix degradation mediated by HT-1080 human fibrosarcoma cells. This inhibition was correlated with an increase in PAI-1 antigen expression, whereas urinary-type plasminogen activator (u-PA) secretion was unaffected. In this experimental system, PAI-1 regulated extracellular matrix breakdown, as added PAI-1 inhibited matrix solubilization, whereas monoclonal antibodies to PAI-1 increased it. A cell line (LPAI) producing high levels of biologically active PAI-1 was established by transfection of a human PAI-1 cDNA clone into mouse L cells. Coculture experiments demonstrated that LPAI cells prevented matrix degradation by Lu-PA cells (L cells expressing high levels of u-PA) or Co-115 human colon carcinoma cells (expressing tissue-type plasminogen activator). These results indicate that PAI-1 may play a critical role in the regulation of extracellular matrix degradation during tumor cell invasion.

Animals↗
PubMed1992

Suramin is an inhibitor of DNA topoisomerase II in vitro and in Chinese hamster fibrosarcoma cells.

The antitrypanosomal and antifiliarial drug suramin is currently under investigation for treatment of advanced malignancies including prostatic cancer, adrenocortical cancer, and some lymphomas and sarcomas. Here we show that suramin is a potent inhibitor of the nuclear enzyme DNA topoisomerase II. Suramin inhibited purified yeast topoisomerase II with an IC50 of about 5 microM, as measured by decatenation or relaxation assays. Suramin did not stabilize the covalent DNA-topoisomerase II reaction intermediate ("cleavable complex"), whereas other inhibitors of this enzyme, such as amsacrine, etoposide, and the ellipticines, are known to stabilize the intermediate. In contrast, the presence of suramin strongly inhibited the cleavable-complex formation induced by amsacrine or etoposide. Accumulation of the endogenous cleavable complex was also inhibited. Suramin entered the nucleus of DC-3F Chinese hamster fibrosarcoma cells exposed to radiolabeled suramin for 24 hr as shown by both optic and electron microscopy. The suramin present in the nucleus seemed to interact with topoisomerase II, since suramin reduced the number of amsacrine-induced protein-associated DNA strand breaks in DC-3F cells and protected these cells from the cytotoxic action of amsacrine. Cells resistant to 9-hydroxyellipticine, which have been shown to have an altered topoisomerase II activity, are about 7-fold more resistant to suramin than the sensitive parental cells as shown by 72-hr growth inhibition assay. Our results suggest that DNA topoisomerase II is a target of suramin action and that this action may play a role in the cytotoxic activity of suramin.

Amsacrine↗
PubMed1996

Inhibition of tumor progression by suppression of stress protein GRP78/BiP induction in fibrosarcoma B/C10ME.

Stress protein GRP78/BiP is highly induced in progressively growing tumors and has recently been shown to exert a protective role against lysis by cytotoxic T cells and tumor necrosis factor in vitro. This raises the question whether the in vitro observed protective function of GRP78/BiP translates into the in vivo situation in which tumors grow progressively, killing the host. Herein we report that molecular inhibition of GRP78/BiP induction in the fibrosarcoma B/C10ME, while not affecting in vitro cell proliferation, causes a dramatic increase in apoptotic cell death upon Ca2+ depletion of the endoplasmic reticulum. When B/C10ME cells incapable of inducing GRP78/BiP are injected into mice, tumors are initially formed that, however, regress presumably due to a cytotoxic T-cell response demonstrable by a strong in vitro response to the tumor with spleen cells of regressor mice. Since sensitivity to apoptosis is key to tumor rejection, these results may point to new approaches to the therapy of cancer via regulation of stress protein GRP78/BiP.

Animals↗
PubMed1998

A human fibrosarcoma inhibits systemic angiogenesis and the growth of experimental metastases via thrombospondin-1.

Concomitant tumor resistance refers to the ability of some large primary tumors to hold smaller tumors in check, preventing their progressive growth. Here, we demonstrate this phenomenon with a human tumor growing in a nude mouse and show that it is caused by secretion by the tumor of the inhibitor of angiogenesis, thrombospondin-1. When growing subcutaneously, the human fibrosarcoma line HT1080 induced concomitant tumor resistance, preventing the growth of experimental B16/F10 melanoma metastases in the lung. Resistance was due to the production by the tumor cells themselves of high levels of thrombospondin-1, which was present at inhibitory levels in the plasma of tumor-bearing animals who become unable to mount an angiogenic response in their corneas. Animals carrying tumors formed by antisense-derived subclones of HT1080 that secreted low or no thrombospondin had weak or no ability to control the growth of lung metastases. Although purified human platelet thrombospondin-1 had no effect on the growth of melanoma cells in vitro, when injected into mice it was able to halt the growth of their experimental metastases, providing clear evidence of the efficacy of thrombospondin-1 as an anti-tumor agent.

Animals↗
PubMed1995

Release of gelatinase A (matrix metalloproteinase 2) induced by photolysis of caged phosphatidic acid in HT 1080 metastatic fibrosarcoma cells.

Phosphatidic acid (PA) is a putative novel messenger in signal transduction and membrane traffic. We have synthesized a photolyzable derivative of PA, termed caged PA (cPA), which may be utilized as a new tool in studies of PA-mediated cellular events. 1-(2-Nitrophenyl)diazoethane, synthesized from 2-nitroacetophenone, was reacted with dipalmitoyl-PA to yield a 1-(2-nitrophenyl)ethyl ester of PA. Photolysis of the compound by ultraviolet light resulted in the formation of phosphatidic acid. The structure of the compound and of its photolytic products was verified by NMR spectroscopy. The utility of cPA was examined in HT 1080 metastatic fibrosarcoma cells, in which the formation of PA by phospholipase D was implicated in laminin-induced release of gelatinase A (matrix metalloproteinase 2 (MMP-2)). The uptake of cPA by HT 1080 cells reached a plateau after 120 min of incubation. Ultraviolet illumination of cPA-loaded cells for 5 s resulted in photolysis of 1.8% of the cell-incorporated cPA. The photolysis of cPA caused a 2-fold elevation in the release of MMP-2 to the medium, whereas nonphotolyzed cPA caused no change in MMP-2 release. Moreover, the effect of cPA photolysis was significantly higher than that obtained with extracellularly introduced PA. Thus, the effect of laminin on MMP-2 secretion can be mimicked by photolysis of cPA, suggesting a pivotal role for phospholipase D in laminin-induced cancer cell invasiveness and metastasis. These results indicate that cPA could serve as a unique tool for studying the cellular roles of PA.

Cell Line↗
PubMed1996

Manganese superoxide dismutase modulates interleukin-1alpha levels in HT-1080 fibrosarcoma cells.

Reactive oxygen species of mitochondrial origin have been implicated in regulating the expression of several tumor necrosis factor (TNF)-induced genes. Manganese superoxide dismutase (Mn-SOD) is one of many genes, but only antioxidant enzyme, induced in response to tumor necrosis factor. Mn-SOD is a nuclear-encoded mitochondrial matrix protein and serves a protective function by detoxifying superoxide. To address the role of superoxide in regulating gene expression in response to TNF, we have constitutively overexpressed Mn-SOD in a human fibrosarcoma cell line and asked what effect this has on the expression of a number of TNF-responsive genes using reverse transcription-polymerase chain reaction. Of the TNF-induced transcripts analyzed, only interleukin-1alpha (IL-1alpha) was modulated in response to Mn-SOD overexpression. In all cases of Mn-SOD overexpression, IL-1alpha protein and mRNA levels were lowered constitutively and in response to TNF when compared to the parental and mock-transfected cell lines. The induction of IL-1alpha by TNF can also be decreased by growth in 3% oxygen as compared to growth in 21% O2; in addition, growth in low oxygen lowers the basal level of IL-1alpha protein. The effect of Mn-SOD overexpression on IL-1alpha expression can be overcome by treatment with the protein kinase C activator, phorbol 12-myristate 13-acetate. Mn-SOD overexpression and low oxygen alter IL-1alpha mRNA levels by decreasing the stability of the IL-1alpha mRNA. These findings indicate that both Mn-SOD and O2 may regulate the levels of a cellular oxidant involved in both basal and TNF-induced IL-1alpha expression, presumably superoxide.

Base Sequence↗
PubMed1997

Urokinase plasminogen activator and gelatinases are associated with membrane vesicles shed by human HT1080 fibrosarcoma cells.

Membrane vesicles are shed by tumor cells both in vivo and in vitro. Although their functions are not well understood, it has been proposed that they may play multiple roles in tumor progression. We characterized membrane vesicles from human HT1080 fibrosarcoma cell cultures for the presence of proteinases involved in tumor invasion. By gelatin zymography and Western blotting, these vesicles showed major bands corresponding to the zymogen and active forms of gelatinase B (MMP-9) and gelatinase A (MMP-2) and to the MMP-9. tissue inhibitor of metalloproteinase 1 complex. Both gelatinases appeared to be associated with the vesicle membrane. HT1080 cell vesicles also showed a strong, plasminogen-dependent fibrinolytic activity in 125I fibrin assays; this activity was associated with urokinase plasminogen activator, as shown by casein zymography and Western blotting. Urokinase was bound to its high affinity receptor on the vesicle membrane. Addition of plasminogen resulted in activation of the progelatinases associated with the vesicles, indicating a role of the urokinase-plasmin system in MMP-2 and MMP-9 activation. We propose that vesicles shed by tumor cells may provide a large membrane surface for the activation of membrane-associated proteinases involved in extracellular matrix degradation and tissue invasion.

Blood↗
PubMed1999

Phospholipase D mediates matrix metalloproteinase-9 secretion in phorbol ester-stimulated human fibrosarcoma cells.

Phospholipase D (PLD) has been implicated in vesicle trafficking in the Golgi and hence secretion. In this study, we show that the secretion of matrix metalloproteinase-9 (MMP-9) from HT 1080 human fibrosarcoma cells was stimulated by phorbol 12-myristate 13-acetate in a time- and dose-dependent manner that involved protein kinase C. The phorbol ester also increased PLD activity in the cells. Evidence that PLD was involved in the stimulation of MMP-9 secretion was provided by the observations that the secretion of MMP-9 was stimulated by the introduction of short-chain phosphatidic acid (PA) into the growth medium and that inhibition of PA production by 1-propanol inhibited secretion. Using a short-chain diacylglycerol we excluded the possibility that MMP-9 secretion was induced by diacylglycerol formed from PA by phosphatidic acid phosphatase. Furthermore, propranolol, an inhibitor of this enzyme, had no effect on secretion induced by either phorbol 12-myristate 13-acetate or PA. The data presented here indicate that activation of protein kinase C increases MMP-9 secretion in HT 1080 cells and implicate PLD and PA formation in the effect.

Collagenases↗
PubMed1999

The transcription factor EGR-1 suppresses transformation of human fibrosarcoma HT1080 cells by coordinated induction of transforming growth factor-beta1, fibronectin, and plasminogen activator inhibitor-1.

Re-expression of EGR-1 in fibrosarcoma HT1080 suppresses transformation including tumorigenicity (Huang, R.-P., Liu, C., Fan, Y., Mercola, D., and Adamson, E. (1995) Cancer Res. 55, 5054-5062) owing in part to up-regulation of the transforming growth factor (TGF)-beta1 promoter by EGR-1 which suppresses growth by an autocrine mechanism (Liu, C., Adamson, E., and Mercola, D. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 11831-11836). Here we show that enhanced cell attachment contributes to the suppression via increased secretion of fibronectin (FN) and also of plasminogen activator inhibitor-1 (PAI-1). The secretion of FN and PAI-1 is strongly correlated with EGR-1 expression (RPEARSON = 0.971 and 0. 985, respectively). Addition of authentic TGF-beta1 to parental cells greatly stimulated secretion of PAI-1 but not FN, whereas addition of TGF-beta antibody or lipofection with specific antisense TGF-beta1 oligonucleotides to EGR-1-regulated cells completely inhibits the secretion of PAI-1 but not FN. However, in gel mobility shift assays pure EGR-1 or nuclear extracts of EGR-1-regulated cells specifically bind to two GC-rich elements of the human FN promoter at positions -75/-52 and -4/+18, indicating that the increased secretion of FN is likely due to direct up-regulation by EGR-1. Moreover, adhesion was greatly enhanced in EGR-1-regulated cells and was reversed by treatment with Arg-Gly-Asp (RGD) or PAI-1 antibody indicating that the secreted proteins are functional. We conclude that EGR-1 regulates the coordinated expression of gene products important for cell attachment ("oikis" factor) and normal growth control.

Cell Adhesion↗