Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to investigate the presence of lactotransferrin receptor on breast non-malignant SV-40 immortalized cells (HBL100 and NB54T), benign mastopathy immortalized cells (NPM14T and NPM21T1), hst oncogene transformed HBL100 cell line (tumorigenic HH9 cells) and breast carcinoma cells (T47D, MCF7, VHB1, BT20 and MDA-MB 231). Flow cytometry analyses of the reversible binding of lactotransferrin labeled on its glycan moiety with fluorescein indicate, for the first time, that all these epithelial breast cell lines, express a specific lactotransferrin receptor. The binding parameters of [125I]-lactotransferrin to non-malignant cells, hst oncogene transformed cells and benign mastopathy cells are of the same order of magnitude as those determined for activated lymphocytes and for cancerous breast cell lines, except for MDA-MB 231 cells. MDA-MB 231 cells bind lactotransferrin with the lowest affinity and, in contrast to other analyzed breast cells, are not recognized by antibodies directed against lymphocyte lactotransferrin receptor. These results suggest that MDA-MB 231 lactotransferrin receptor is different from that characterized at the cell surface of other breast cells. In conclusion, since the lactotransferrin receptor expression was not enhanced at the surface of cancerous cell lines and was not altered by the oncogene transformation of a normal cell (HBL100) to a tumorigenic cell (HH9), the lactotransferrin receptor cannot be considered as a marker of tumor progression.
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PMID:Characterization of lactotransferrin receptor in epithelial cell lines from non-malignant human breast, benign mastopathies and breast carcinomas. 133 74

The effects of toremifene, an antiestrogen, and its two main metabolites (4-hydroxy- and N-desmethyltoremifene) on cell proliferation have been tested in a series of breast cancer cell lines, with positive (MCF7, ZR 75.1, T47D, 734B) or negative steroid receptor status (MDA-MB 231, BT20). Drug effects were evaluated at concentrations similar to those obtained in breast cancer patients on toremifene treatment, and in the presence or absence of estradiol. Results showed that, for both positive and negative cell lines, high concentrations of the antiestrogens (10(-6)M) were inhibitory, while lower doses (10(-7)M, 10(-8)M) were stimulatory. These data confirm the biphasic behaviour of toremifene and its derivatives. In terms of a clinical application of toremifene, these results seem to suggest that while high doses of toremifene and its derivatives might be therapeutic, lower concentrations might stimulate cell growth and enhance tumor progression.
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PMID:Effects of toremifene and its main metabolites on growth of breast cancer cell lines. 183 81

TGF-beta effects on angiogenesis, stroma formation, and immune function suggest its possible involvement in tumor progression. This hypothesis was tested using the 2G7 IgG2b, which neutralizes TGF-beta 1, -beta 2, and -beta 3, and the MDA-231 human breast cancer cell line. Inoculation of these cells in athymic mice decreases mouse spleen natural killer (NK) cell activity. Intraperitoneal injections of 2G7 starting 1 d after intraperitoneal inoculation of tumor cells suppressed intraabdominal tumor and lung metastases, whereas the nonneutralizing anti-TGF-beta 12H5 IgG2a had no effect. 2G7 transiently inhibited growth of established MDA-231 subcutaneous tumors. Histologically, both 2G7-treated and control tumors were identical. Intraperitoneal administration of 2G7 resulted in a marked increase in mouse spleen NK cell activity. 2G7 did not inhibit MDA-231 primary tumor or metastases formation, nor did it stimulate NK cell-mediated cytotoxicity in beige NK-deficient nude mice. Finally, serum-free conditioned medium from MDA-231 cells inhibited the NK cell activity of human blood lymphocytes. This inhibition was blocked by the neutralizing anti-TGF-beta 2G7 antibody but not by a nonspecific IgG2. These data support a possible role for tumor cell TGF-beta in the progression of mammary carcinomas by suppressing host immune surveillance.
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PMID:Anti-transforming growth factor (TGF)-beta antibodies inhibit breast cancer cell tumorigenicity and increase mouse spleen natural killer cell activity. Implications for a possible role of tumor cell/host TGF-beta interactions in human breast cancer progression. 750 87

Previous studies demonstrated that metastatic MDA-MB-435 breast carcinoma cells synthesized and secreted less of the extracellular matrix protein thrombospondin 1 (TSP1) than nonmetastatic breast carcinoma cell lines, a trend also observed for melanoma and lung carcinoma cell lines. To directly examine the effect of tumor cell TSP1 expression on tumor growth and metastasis. MDA-MB-435 cells were transfected with full length THBS-1 cDNA linked to a constitutive cytomegalovirus promoter, or with the cytomegalovirus vector alone. Injection of transfected clones that overexpressed TSP1 into the mammary fat pad of nude mice resulted in a dose-dependent inhibition of primary tumor size and an inhibition of spontaneous pulmonary metastases, which occurred in 21-30% of THBS-1 transfectants compared to 44-49% of controls (P = 0.007). An additional clone was identified that overexpressed a COOH-terminally truncated TSP1. This clone produced larger primary tumors and an increase in the occurrence of metastases relative to control transfectants, suggesting the participation of a previously understudied region of TSP1 in the regulation of tumor progression. The THBS-1 and control transfectants did not exhibit significant differences in growth, colonization, or motility in vitro. However, a relative reduction in capillary densities in primary tumors formed by the wild-type THBS-1 transfectants was observed, suggestive of an angiostatic effect. The data indicate that tumor cell production of TSP1 can exert a significant inhibitory effect on tumor progression in the MDA-MB-435 breast carcinoma cell line, which may be attributable in part to a reduction in angiogenesis.
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PMID:Transfection of thrombospondin 1 complementary DNA into a human breast carcinoma cell line reduces primary tumor growth, metastatic potential, and angiogenesis. 752 99

Oncostatin M (OSM) and leukemia inhibitory factor (LIF) are involved in stimulation of acute-phase protein during inflammatory processes. We recently suggested that these two cytokines may play a role in human immune surveillance during tumor progression. The present study was designed to determine the capacity of OSM in modulating LIF production by human tumor cells and to provide a better definition of the interactions between these two molecules during inflammatory reaction due to neoplasia. LIF content in culture supernatants was assayed by a specific ELISA (sensitivity: 25 pg/ml). In vitro exposure to recombinant OSM increased LIF production 2 to 6-fold in all human melanoma cell lines tested. This effect was not limited to melanoma cell types since LIF production was also enhanced by an MDA breast undifferentiated adenocarcinoma line. Moreover, a synergistic effect was observed for OSM and TNF-alpha. LIF increase was apparently due to up-modulation through LIF synthesis since LIF transcript expression was also enhanced in these tumor cell lines. It is concluded that OSM can induce inflammatory reaction not only directly but also via LIF production by tumor cells.
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PMID:Modulation of LIF expression in human melanoma cells by oncostatin M. 759 Sep 43

The biological significance of a major protein component in the fluid of gross cystic breast disease and a recognized marker of apocrine metaplasia, i.e. the 15-kDa glycoprotein (GCDFP-15), is presently unknown. We have added GCDFP-15 to cell culture medium and tested its effect on proliferation of 4 human breast-cancer cell lines (MCF7, BT474, MDA-MB231 and T47D) and a "normal" human immortal breast-cell line (MCF10A). These breast-cell lines showed a mitogenic response to GCDFP-15 (10 micrograms/ml). GCDFP-15 enhanced cell growth of the MCF10A, MCF7, BT474 and MDA-MB231 cell lines at both 48 and 96 hr of exposure. The glycoprotein exerted a mitogenic effect on the T47D cell line at 48 hr but not at 96 hr. This may be due to an auto-regulatory effect of endogenous GCDFP-15 synthesized by the T47D cells. GCDFP-15 was ineffective on 2 colon-cancer cell lines (HT29 and NIC-H716), on the IMR32 neuroblastoma cell line and on the NIC-H209 small-cell lung carcinoma cells. A separate major breast cystic disease fluid protein of 24 kDa (GCDFP-24) was tested, following the same experimental design, on the 5 breast-cell lines, and showed no mitogenic activity. The mitogenic effect of GCDFP-15 observed in this study in both "normal" and malignant breast epithelial cells suggests a possible relationship between apocrine metaplasia in breast cystic disease and the development of breast epithelial hyperplasia. In addition, a possible role of GCDFP-15 in breast-cancer progression should be considered.
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PMID:Mitogenic effect of the 15-kDa gross cystic disease fluid protein (GCDFP-15) on breast-cancer cell lines and on immortal mammary cells. 782 19

Osteopontin (OPN), a secreted phosphoprotein, has been implicated in various biological phenomena (e.g. bone development, sepsis, tumor progression, and metastasis). Its role in any context is poorly understood. OPN contains a conserved Gly-Arg-Gly-Asp-Ser (GRGDS) sequence, and binds to cells via integrin-mediated mechanisms. Using recombinant human osteopontin-glutathione S-transferase fusion protein and our improved hybridoma fusion partner (Sp2/mIL6), we raised murine monoclonal antibodies against osteopontin. We characterized two antibodies that recognize not only recombinant but also native human osteopontin. These antibodies do not cross-react with mouse osteopontin (recombinant protein or that secreted by ras-transformed NIH 3T3 cells), or bovine bone osteopontin, suggesting that they recognize epitopes unique to human OPN. One antibody specifically inhibited adhesion of MDA-MB-435 human breast cancer cells and ras-transformed NIH 3T3 cells to human osteopontin. This antibody failed to recognize osteopontin cleaved by thrombin, which cleaves adjacent to the cell binding domain. We previously showed that thrombin cleavage reduces osteopontin cell binding activity. Thus we postulate that this monoclonal antibody recognizes and interferes with the function of the RGD/thrombin cleavage region of human OPN.
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PMID:Inhibition of Arg-Gly-Asp (RGD)-mediated cell adhesion to osteopontin by a monoclonal antibody against osteopontin. 808 34

Hepatocyte growth factor/scatter factor (HGF/SF) is a stromally derived modulator of epithelial cell proliferation and morphology. To better assess the potential role of HGF/SF in tumor progression we sought to identify factors and biological conditions which regulate its expression. We show that several adult human primary fibroblast cultures from breast and prostate produce HGF/SF. HGF expression in the MRC-5 human fetal lung fibroblast cell line is stimulated by conditioned media harvested from human breast tumor cell lines (MCF-7, T47D, and MDA-MB-231). In contrast, both indirect and direct coculture of each of these tumor lines with MRC-5 fibroblasts down-regulates HGF/SF expression. Finally, we show that MRC-5 HGF expression is inhibited by several known peptide growth factors, including transforming growth factor beta, epidermal growth factor, and transforming growth factor alpha.
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PMID:Regulation of fibroblast hepatocyte growth factor/scatter factor expression by human breast carcinoma cell lines and peptide growth factors. 844 2

In order to invade and spread cancer cells must degrade extracellular matrix proteins. This degradation is catalysed by the concerted action of several enzymes, including the serine protease plasmin. Several experimental studies have shown that inhibition of plasmin formation reduces cancer cell invasion and metastasis, indicating a critical role of this proteolytic pathway in these processes. In order to further study the role of plasmin in cancer progression, we have characterized urokinase-type plasminogen activator (uPA) mediated plasmin formation in three human breast cancer cell lines. Using monoclonal antibodies against uPA and its receptor uPAR, we have investigated the contribution of uPA and uPAR to invasive capacity in an in vitro invasion assay. MDA-MB-231 BAG cells were found to express high protein levels of uPA, uPAR and PAI-1. MDA-MB 435 BAG cells produced low amounts of uPA, PAI-1 and moderate amounts of uPAR, whereas MCF-7 BAG cells showed low levels of uPA, uPAR and PAI-1 protein. In a plasmin generation assay MDA-MB-231 BAG cells were highly active in mediating plasmin formation, which could be abolished by adding either an anticatalytic monoclonal antibody to uPA (clone 5) or an anti-uPAR monoclonal antibody (clone R3), which blocks binding of uPA to uPAR. The two other cell lines lacked the capacity to mediate plasmin formation. In the Matrigel invasion assay the cells showed activity in this order: MCF-7 BAG < MDA-MB-435 BAG < MDA-MB-231 BAG. Testing MDA-MB-231 BAG cells in the Matrigel invasion assay revealed that invasion could be inhibited in a dose-dependent manner either by the clone 5 uPA antibody or by the clone R3 uPAR antibody, suggesting that the cell surface uPA system is actively involved in this invasive process. It is concluded that these three cell lines constitute a valuable model system for in vitro studies of the role of cell surface uPA in cancer cell invasion and has application in the search for novel compounds which inhibit mechanisms involved in uPA-mediated plasmin generation on cancer cells.
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PMID:Urokinase-type plasminogen activation in three human breast cancer cell lines correlates with their in vitro invasiveness. 867 84

Tumor invasion and metastasis are processes poorly understood at the molecular level. Maspin is a serine protease inhibitor (serpin) with tumor-suppressing function in the mammary gland. Maspin gene expression is decreased with malignancy and is lost in metastatic cells. We show in this report that differential expression of maspin in normal and carcinoma-derived mammary epithelial cells is regulated at the transcriptional level. We have identified the Ets and Ap1 sites in the maspin promoter that are active in regulating maspin expression in normal mammary epithelial cells but inactive in tumor cells. The Ets site alone is sufficient to activate transcription in a heterologous promoter, whereas the Ap1 site cooperates with Ets in activation. The enhancing function by Ets and Ap1 elements is decreased in primary tumor cells (21NT) and is abolished in invasive tumor cells (MDA-231). Thus, loss of maspin expression during tumor progression results at least in part from the absence of transactivation through the Ets and Ap1 sites.
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PMID:Transactivation through Ets and Ap1 transcription sites determines the expression of the tumor-suppressing gene maspin. 904 Sep 39


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