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)

This investigation examined the ability of low-metastatic AT-1 and high-metastatic ML and MLL cell lines to adhere to a monolayer of bovine aortic endothelial cells and fibronectin substratum and penetrate a matrigel basement membrane matrix. Cell area, shape factor, and motility as influenced by fibronectin were also examined using these cell lines. The ability of these cells to adhere to fibronectin and traverse matrigel matrix correlated with their metastatic potential. In addition, fibronectin increases cell circularity and reduces cell area as metastatic potential increases within AT-1 to ML or MLL cell lineages.
Invasion Metastasis 1993
PMID:Adhesion and invasion potential of rat prostatic cancer cells: correlation with metastatic potential. 803 39

We report here on treatment results of consecutive CCLSG NHL studies (NHL855, 1985-1989; NHL890, 1989-1996). The NHL855 protocol consisted of an induction phase of five drugs (VCR, PRD, CPM, DXR, and high-dose MTX) and a maintenance phase of 7 drugs. The probabilities of EFS at 7 years were 78% (SE, 10%) for the patients with localized disease, and 38% (SE, 7%) for those with advanced disease. In the NHL 890 protocol, the patients were assigned to two different treatment groups according to their histology and received different consolidation therapy; non-lymphoblastic subtype was treated almost identically to NHL855 while LASP and VP-16 were newly added for the lymphoblastic subtype. The 7-year EFS improved to 91% (SE, 6%) for localized disease, and 61% (SE, 6%) for advanced disease. A remarkable improvement was particularly evident for lymphoblastic type with mediastinal mass. Optional trial of high-dose sequential chemotherapy and peripheral blood progenitor cell auto grafting resulted in an unfavorable outcome. The 7-year EFS according to main histological subgroups were as follows: 84% (10%) for large cell type, 67% (11%) for Burkitt's-type, 58% (10%) for lymphoblastic type. Secondary cancer occurred in two of the 163 patients studied. Both patients were AML (M0/M4) and MLL rearrangement was detected in the M4 case.
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PMID:[Treatment of children with non-Hodgkin's lymphoma with CCLSG NHL 855/890 protocols long-term outcome and incidence of secondary malignancies]. 959 95

Most deaths from cancer result from the metastatic spread of the disease. The antidiuretic amiloride has been shown to inhibit tumor growth and metastasis in several tumor systems. The object of these studies was to examine the effect on the in vitro and in vivo tumor growth and metastasis in the MatLyLu subline of the Dunning model of rat prostate cancer. In vitro, amiloride was found to have cytotoxic effects only at high concentrations, with an IC50 of 100 microg/ml. In vitro analysis of the ability of amiloride to inhibit invasion of MLL cells demonstrated that this drug was ineffective at all concentrations examined. In vivo, amiloride did not inhibit tumor growth or metastases development. Our studies demonstrate that amiloride does not have activity in this model of prostate cancer and suggest it may not be an appropriate therapy for the treatment of prostate cancer.
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PMID:The effect of amiloride on the metastatic properties of prostate cancer in the Dunning rat model. 962 39

Cancer cell attachment to and invasion of the extracellular matrix has been associated with the metastatic potential of cell lines of the Dunning R-3327 rat prostatic adenocarcinoma model. We investigated the cell-matrix interactions of prostate tumor cells by comparing the invasive ability through reconstructed extracellular matrix and attachment upon EHS NATRIX (natural extracellular matrix), fibronectin, laminin, and collagen Type IV. We observed a correlation between metastatic potential and substrate dependence of attachment in prostate cancer cells. Nonmetastatic AT-1 cells possessed a higher adhesive potential to extracellular matrix components than the highly metastatic cells (ML, MLL and AT-3). It was also found that the invasive potential of the three highly metastatic cell lines was significantly higher than that of the nonmetastatic cell line. Here, it is reported that the ability to traverse a matrigel matrix correlates with their metastatic potential. These observations suggest that the extracellular matrix components are highly involved in influencing prostate cancer cell activities. In addition, we investigated the effects of two differentiation agents, retinoic acid (RA) and difluoromethylornithine (DFMO), on the adhesive and invasive profiles of the tumor cells. After treatment with both agents, adhesion was increased to levels not different from nonmetastatic cells. Furthermore, the ability of highly metastatic cells to traverse a matrigel barrier was significantly reduced after treatment with both differentiation agents. These results suggest that RA and DFMO are capable in reversing the metastatic potential of prostate cancer cells in vitro and may give a possible insight into their role as potential therapeutic agents in vivo.
Invasion Metastasis
PMID:Invasive potential and substrate dependence of attachment in the dunning R-3327 rat prostate adenocarcinoma model. 1064 Sep 2

Calcitriol or 1,25-dihydroxycholecalciferol (vitamin D) is classically known for its effects on bone and mineral metabolism. Epidemiological data suggest that low vitamin D levels increase the risk and mortality from prostate cancer. Calcitriol is also a potent anti-proliferative agent in a wide variety of malignant cell types including prostate cancer cells. In prostate model systems (PC-3, LNCaP, DU145, MLL) calcitriol has significant anti-tumor activity in vitro and in vivo. Calcitriol's effects are associated with an increase in cell cycle arrest, apoptosis, differentiation and in the modulation of growth factor receptors. Calcitriol induces a significant G0/G1 arrest and modulates p21(Waf/Cip1) and p27(Kip1), the cyclin dependent kinase inhibitors. Calcitriol induces PARP cleavage, increases the bax/bcl-2 ratio, reduces levels of phosphorylated mitogen-activated protein kinases (P-MAPKs, P-Erk-1/2) and phosphorylated Akt (P-Akt), induces caspase-dependent MEK cleavage and up-regulation of MEKK-1, all potential markers of the apoptotic pathway. Glucocorticoids potentiate the anti-tumor effect of calcitriol and decrease calcitriol-induced hypercalcemia. In combination with calcitriol, dexamethasone results in a significant time- and dose-dependent increase in VDR protein and an enhanced apoptotic response as compared to calcitriol alone. Calcitriol can also significantly increase cytotoxic drug-mediated anti-tumor efficacy. As a result, phase I and II trials of calcitriol either alone or in combination with the carboplatin, paclitaxel, or dexamethasone have been initiated in patients with androgen-dependent and -independent prostate cancer and advanced cancer. Patients were evaluated for toxicity, maximum tolerated dose (MTD), schedule effects, and PSA response. Data from these studies indicate that high-dose calcitriol is feasible on an intermittent schedule, the MTD is still being delineated and dexamethasone or paclitaxel appear to ameliorate toxicity. Studies continue to define the MTD of calcitriol whichcan be safely administered on this intermittent schedule either alone or with other agents and to evaluate the mechanisms of calcitriol effects in prostate cancer.
Cancer Metastasis Rev 2002
PMID:Vitamin D-related therapies in prostate cancer. 1246 54

Up-regulation of extracellular-regulated kinases 1/2 (ERK1/2) has been implicated in tumor progression and metastasis in many types of cancer. We have previously shown that ERK1/2 is necessary for invasiveness of Dunning rat prostatic adenocarcinoma cell lines in which levels of activated ERK1/2 correlate with the metastatic potential. Here, we further examined the biological effects of elevated ERK1/2 in the highly metastatic Dunning cell line, MLL, in which the abilities to invade and metastasize are enhanced relative to its progenitor strain. Inhibition of ERK1/2 activation by the MEK1 inhibitor, PD98059, dose-dependently reduced MLL cell invasiveness and motility with similar IC50 values. On the other hand, the abilities of MLL cells to adhere to the extracellular matrix, phosphorylate myosin regulatory light chain and secrete matrix-degrading enzymes, matrix metalloproteinase (MMP)-2 and urokinase plasminogen activator (uPA) were marginally, if at all, affected by PD98059 treatment. These data indicated that the inhibitory effect of PD98059 on the invasiveness of MLL cells was primarily due to the suppression of cell motility, and the up-regulation of ERK1/2 is, at least in part, responsible for the enhanced cellular motility and invasiveness of the MLL cells.
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PMID:PD98059-inhibited invasion of Dunning rat prostate cancer cells involves suppression of motility but not MMP-2 or uPA secretion. 1668 2

The preferential proliferation of cancer cells in the bone microenvironment is poorly characterised. Expression pattern of bone marrow and other organ microenvironment in contact with osteolytic (Walker W256) and osteoblastic (MatLyLu MLL) metastases were investigated. Fisher and Copenhagen rats received, respectively, W256 and MLL cells injection. Bone and soft tissues were analysed by immunochemistry for DKK1, cathepsin K, RANKL, MCSF or IL6 expression. Tartrate-resistant acid phosphatase (TRAcP)-positive cells were detected by a histoenzymatic technique. In bone, expressions of MCSF and DKK1 were shown in stromal cells of the bone marrow, in contact with metastatic foci of both tumours. Many stromal cells were found RANKL positive in the vicinity of the tumours. Cells expressing cathepsin K and multinucleated TRAcP+ cells were found in direct contact with trabeculae but also in bone marrow spaces near metastatic cells. In extraosseous tumours, cells in contact with malignant cells did not expressed DKK1, MCSF, cathepsin K and IL6. Some RANKL+ cells were found in the periphery of subcutaneous tumours but may represent Langerhans cells. Abnormal presence of TRAcP+ cells was never observed in the vicinity of malignant cells. Interaction between stromal and cancer cells induces the expression on the formers of characteristics leading to osteoclastogenesis only in the bone microenvironment.
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PMID:Interactions between microenvironment and cancer cells in two animal models of bone metastasis. 1825 14

Bone metastases are severe complications of cancers associated with increased morbidity, pain, risk fracture, and reduced life span for patients. Bisphosphonates emerged as a relief treatment in bone metastases. A single dose of zoledronic acid (78 microg/kg) was injected into six Copenhagen rats 4 days before receiving an intraosseous inoculation of metastatic anaplastic tumor of lymph node and lung cell (MLL) prostate cancer cells. Rat femurs were analyzed for changes by microCT and histomorphometry; trabecular volume, trabecular characteristics, osteoid parameters, osteoblastic surfaces, and osteoclast number were measured. Values were compared to a group of SHAM animals, a group of SHAM animals having received zoledronic acid and animals inoculated with MLL cells. All rats were euthanized after 1 month. MLL cells induced osteolysis in the metaphysis with extension of the tumor to soft tissues through cortical perforations. Zoledronic acid induced a marked osteosclerosis in the primary spongiosa in both SHAM and rats inoculated with MLL. Osteosclerosis was obtained in the secondary spongiosa of MLL rats. The bisphosphonate preserved cortical integrity in all animals, and no extension to soft tissues was observed in most animals. The number of osteoclasts was elevated, indicating that there was no apoptosis of osteoclasts but they became inactive. Osteosclerosis was associated with increased osteoblastic surfaces. A single zoledronic acid injection turned osteolytic metastases into osteosclerotic and preserved cortical integrity.
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PMID:A single pretreatment by zoledronic acid converts metastases from osteolytic to osteoblastic in the rat. 1995 66

The transforming growth factor beta, Hedgehog, Notch, and Wnt signaling pathways all play critical roles in the development and progression of prostate cancer. It is becoming increasingly apparent that these pathways may intersect with developmentally important transcription factors such as the sex-determining region Y-box 4 (SOX4), homeobox C6, enhancer of zeste 2, and ETS-related gene, which are up-regulated in prostate cancers. For example, identification of the downstream targets of SOX4 and homeobox C6 suggests that these factors may cooperate to activate the Notch pathway and the PI3K/AKT pathway, possibly in response to Wnt signals. PI3K/AKT activation likely occurs indirectly via up-regulation of growth factor receptors, while Notch activation is secondary to up-regulation of Notch pathway components. In addition, SOX4 may affect terminal differentiation via regulation of other transcription factors such as NKX3.1 and MLL, and regulation of components of the microRNA pathway such as Dicer and Argonaute 1. The evidence supporting activation of these pathways in prostate cancer progression suggests that combinations of compounds targeting them may be of benefit to patients with aggressive, metastatic disease.
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PMID:The Sex-determining region Y-box 4 and homeobox C6 transcriptional networks in prostate cancer progression: crosstalk with the Wnt, Notch, and PI3K pathways. 2001 90

Death from prostate cancer is most frequently a result of metastatic disease. A key step in the process of metastasis is the attachment of circulatory tumor cells to target organ endothelium. This process is thought to be mediated by lectins, a class of cell surface proteins that bind two or more carbohydrate groups. Using fluorescent microscopy and fluorescein isothiocyanate (FITC) conjugated lectins, the presence of various carbohydrates was examined in the following tumorigenic and non-tumorigenic cell lines: rat prostate epithelial (EPYP-2, EPYP-1), rat prostate endothelial (YPEN-2, YPEN-1, YPEN-2PV), Dunning rat prostate cancer cell lines (MLL, ML, AT6.3, AT.1, AT2.1, GP9F3), and three tumorigenic human prostate cell lines (LNCaP, PC3, PC3 bone). The lectin Triticum vulgaris (WGA) was found to readily bind the carbohydrates N-acetylglucosamine and sialic acid on the plasma membrane of tumorigenic cell lines. Interestingly, WGA bound carbohydrates located to the nucleus and cytoplasm in non-tumorigenic cell lines, indicating that N-acetylglucosamine and sialic acid residues are preferentially expressed on the cell membrane of prostate cancer cells. Lectin staining patterns in cell lines of varying metastatic potential revealed no significant difference between highly metastatic vs. low metastatic cell lines. Observations revealed an absence of N-acetylgalactosamine and L-fucose in all rat Dunning, epithelial and endothelial cell lines as well as all human prostate cancer cell lines except for the androgen insensitive human prostate cancer cell line PC3, in which L-fucose residues were detected in the nucleus and on the plasma membrane. PC3 bone cells, which metastasized selectively to bone, demonstrated the presence of galactose residues whereas PC3 cells did not, suggesting that preference for target organ endothelium may be influenced by the expression of carbohydrate residues. These data indicate that differential carbohydrate expression may play an important role in prostate cancer biology.
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PMID:Differential carbohydrate expression in tumorigenic vs nontumorigenic prostate cell-lines. 2155 71


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