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)

Retroviral oncogenes are genetic elements, the expression of which is responsible for the transformed phenotype of cells. These genes are derived from normal cellular DNA sequences called cellular protooncogenes, which are present in all human cells and seem to have potential transforming ability in tumors of nonviral origin, since it is possible that they undergo structural alterations and/or changes in their expression. Human skin tumors were analyzed in this study with respect to the expression of the c-src protooncogene, the cellular homologue of the Rous sarcoma virus transforming gene, by measuring the enzymatic activity of its gene product, the pp60c-src kinase activity. Tyrosine-specific kinase activity was detected in all skin tumors tested. The expression pattern of the c-src gene product in the melanomas tested was differential and varying kinase levels in different metastases from the same patient were detected. The elevation of kinase activity as compared to normal skin ranged from about 4- to 20-fold.
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PMID:Expression of the c-src protooncogene in human skin tumors. 243 64

The myoepithelial-type cell line, Rama 712, derived from a normal rat mammary gland, deposits an extracellular matrix containing type-IV collagen and other basement membrane proteins round its cellular periphery. After transformation with a temperature-sensitive mutant of Rous sarcoma virus (tsRSV) the cells fail to deposit an extracellular matrix at the permissive temperature (35 degrees C), but retain the capacity to do so at the non-permissive temperature (41 degrees C). The synthesis of type-IV collagen is not affected by the temperature shift. Rama 712 cells fail to form tumours in syngeneic rats. However, Rama 712-tsRSV cells form tumours that are locally invasive but fail to metastasize. In histological sections, the tumour cells stain with an antibody to type-IV collagen, but do not deposit any extracellular type-IV collagen. Cells isolated from the tumours (Rama 712T) remain temperature-sensitive for the extracellular deposition of type-IV collagen when grown in vitro. Rama 712, Rama 712-tsRSV and Rama 712T fail to produce any detectable type-I or type-IV collagenase at either 35 degrees C or 41 degrees C. These results show that in this system extracellular deposits of basement membrane proteins are lost from invasive tumours produced by myoepithelial-type cells by mechanisms other than those due to the production of collagenolytic enzymes.
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PMID:Loss of basement membrane deposits and development of invasive potential by virally-transformed rat mammary cells are independent of collagenase production. 303 59

A number of studies show that major histocompatibility complex (MHC) genes control host immune responses to viral-induced chicken tumors. The MHC gene-controlled responses to malignant neoplasms caused by Rous sarcoma virus, lymphoid leukosis virus and Marek's disease virus are reviewed. Genes that determine regression of Rous sarcomas and resistance to development of lethal Marek's disease lymphomas appear to map within the B-F region of the MHC. In some cases, genetic complementation of both MHC genes and non-MHC genes may be responsible for regression of tumors. Metastasis of Rous sarcoma cells is also influenced by the host's MHC genotype. Background genes can modify the specific MHC gene effect on resistance to progressive growth of Rous sarcomas and Marek's disease lymphomas. Studies showing that MHC-restricted immunity may be important in cytotoxic T cell reactions to virus-infected and/or transformed chicken cells are discussed. The MHC-restricted cytotoxicity, whereby the T cells and target cells must share one MHC haplotype for in vitro killing to occur, suggests that the T cells have receptors that recognize virus-altered self MHC antigens. This may be an important immune surveillance mechanism for limiting the proliferative growth of virus-induced tumors in chickens.
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PMID:Influence of the major histocompatibility complex on tumor regression and immunity in chickens. 330 46

Alterations in the adhesive mechanisms of cancer cells are likely to play an important role in determining the invasive or metastatic potential of these cells. An understanding of these alterations at the molecular level is now within reach, due to recent progress in the identification and characterization of several cell adhesion molecules (CAMs). Two of these molecules, the neural cell adhesion molecule N-CAM and the liver cell adhesion molecule L-CAM, are expressed on a variety of cell types from early embryos and throughout adult life, and appear to play several important roles in early inductive events, formation of specific intercellular connections, and maintenance of adult tissues. Two other molecules, the neuron-glia adhesion molecule Ng-CAM and a molecule involved in the specific adhesion of lymphocytes, appear to be more restricted in their developmental expression and function. The molecular characterization of N-CAM made possible for the first time an examination of the effects of transformation on the expression of a defined cell adhesion molecule. In both established cell lines from rat cerebellum and embryonic chick neuroepithelial cells, transformation by Rous sarcoma virus caused a large reduction in expression of N-CAM. In both cases, the N-CAM-mediated adhesion was correspondingly reduced. The neuroepithelial cells also became more highly motile after transformation. The decrease in N-CAM coupled with this increase in cell motility may significantly enhance the invasiveness of these cells. Other surface antigens have also been identified that may be involved in essential steps of invasion and metastasis. Such studies represent the initial step toward a detailed understanding of the role of CAMs in the various steps of metastasis. The accessibility of CAMs on tumor cell surfaces, and the availability of specific antibodies to these components suggests that reagents may become available in the near future that will offer new opportunities for preventing the formation of metastases.
Cancer Metastasis Rev 1985
PMID:Molecular mechanisms of cell adhesion in normal and transformed cells. 388 82

Response to Rous sarcoma virus (RSV)-induced tumors was studied in Regional Poultry Research Laboratory (RPRL) lines 61, 63, 72, 100, 151, and 15I5 and in Reaseheath line C, all highly inbred White Leghorn stocks. Virus inoculations were made in chickens at 6 weeks of age. Tumors were scored subjectively for size on a regular basis and in some instances a tumor profile index (TPI) was assigned which characterized tumor development over a 10 week period for each chicken (TPI 1 = complete regression in 28 days; TPI 5 = terminal tumor). The frequency of tumor regression, terminal tumors, and metastases and mean TPI was examined. The incidence of tumor regression ranged from 92% in line 61 to 0 % in lines 151 and 15I5. The frequency of terminal tumors varied from 100% in line 151 to 2% in line61, while metastasis in chickens with terminal tumors differed from 92% in line 15I5 to 0% in line 61. Mean TPI ranged from 2.0 in line 61 to 4.6 in line 15I5 and 4.7 in line C. The erythrocyte alloantigen genotype at the B blood group locus, (part of the B complex, MHC) and 11 additional blood group loci were known for each of the lines. The data indicate that genetic differences in tumor regression may be pronounced between inbred lines which share similar, if not identical, B locus erythrocyte alloantigens and that other unknown genes are also involved.
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PMID:Rous sarcoma regression in seven highly inbred lines of White Leghorns. 625 Jan 36

The correlation between metastatic potential and a series of biological properties was investigated in two mouse fibrosarcoma lines (SR-BALB and B77-3T3), transformed by different strains of Rous sarcoma virus (RSV). In the absence of selective pressure the metastatic potential was different in the two lines. The SR-BALB sarcoma did produce both spontaneous metastases from s.c. site and i.v. lung colonization with a high incidence (respectively in 60% and 80% of treated animals). Conversely, the metastatic incidence of the B77-3T3 sarcoma was much lower. Differences in lung implantation between the two lines turned out to be even greater when the number of colonies growing in the lung was evaluated. Organ distribution of cells after i.v. injection, tumorigenicity, growth rate in vivo and in vitro, plating efficiency in liquid medium and cloning efficiency in semi-solid agar medium were evaluated in the two lines. A strict correlation was found only between the metastatic potential and the capability of growth in 0.6% ("hard") agar. Such a correlation was supported by the isolation in "hard" agar of highly metastasizing subclones of the low-metastasizing B77-3T3 line.
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PMID:Characterization of stable spontaneous metastatic variant lines of RSV-transformed mouse fibroblasts. 629 21

The metastatic capability of cells at the initial stages of selection for "typical" (P-glycoprotein-mediated) multidrug resistance (MDR) was studied. Two independent sublines, 2SC/4-1 and 2SC/4-2 (11-12.4-fold resistant), and their 23- to 23.7-fold resistant 2SC/20-1 and 2SC/20-2 variants were isolated from highly tumorigenic (TrD50 = 10 cells) and highly metastatic Rous sarcoma, virus-transformed Syrian hamster fibroblast HET-SR-2SC-LNM line for resistance to colchicine. 2SC/4 cells were less tumorigenic (TrD50 = 70 cells) but as highly metastatic as parental counterparts. In contrast, both 2SC/20 variants showed a decrease in tumorigenicity (TrD50 = 320 cells) and in the capability to produce spontaneous distant metastases. 2SC/20 cells almost lost the ability to colonize lungs in experimental metastasis assay. The autophosphorylation of pp60src tyrosine kinase in 2SC/20 cells was unaltered. The results suggest that i) selection of tumor cells for low levels of "typical" MDR leads to a decrease in the frequency of spontaneous and experimental metastases, and ii) alterations of malignancy in these cells are not caused by an impairment of function of a transforming oncogene.
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PMID:Frequency of metastasis in Syrian hamster tumor cells selected for low levels of "typical" multidrug resistance. 752 75

The WC5 rat cerebellar cell line, infected with a Rous sarcoma virus (RSV) that is temperature-sensitive for pp60v-src transformation, expresses high levels of the neural cell adhesion molecule, N-CAM, when grown at the non-permissive temperature for pp60v-src activity. At the permissive temperature, N-CAM expression is 4- to 10-fold reduced and the cells aggregate poorly. To evaluate the effects of variations in N-CAM expression, we compared the invasive ability of transformed WC5 cells that express low levels of N-CAM with transformed cells in which N-CAM-mediated adhesion was restored. WC5 cells were transfected with expression vectors containing cDNAs encoding the 120 or 180 kDa forms of chicken N-CAM linked to constitutive promoters. Several permanently transfected lines that expressed chicken N-CAM at the cell surface were isolated. These cell lines showed enhanced aggregation at the permissive temperature relative to untransfected WC5 cells or cells transfected with control constructs. By comparing the ability of control and transfected WC5 cells to invade reconstituted extracellular matrix, we tested the effect of variations in N-CAM-mediated adhesion on invasion. Clones that expressed high levels of N-CAM showed invasion rates that were similar to control cells, indicating that increasing N-CAM-mediated adhesion does not inhibit the invasiveness of RSV-transformed WC5 cells.
Clin Exp Metastasis 1993 Jul
PMID:Increasing N-CAM-mediated cell-cell adhesion does not reduce invasion of RSV-transformed WC5 rat cerebellar cells. 839 6

A transforming growth factor beta1 (TGF beta1) antisense expression plasmid under constitutive control of the Rous sarcoma virus promoter was introduced into the highly tumorigenic and invasive colon carcinoma U9A cell line, which uses its autocrine TGF beta1 as a growth-stimulating factor. Stable transfectants were infrequent, and only the K6 transfectant exhibited 39 and 33%, respectively, of the levels of TGF beta1 mRNA and active, secreted TGF beta1 protein of the parental line. K6 exhibited no change in TGF beta2 expression, and TGF beta3 expression was not detected in either parental or transfectant cells. Compared to the parental line, the K6 antisense transfectant exhibited a 3-fold increase in lag time in anchorage-dependent colony formation. The parental line was 44 times as invasive through a collagen l-coated polycarbonate membrane in vitro as K6 cells and, after s.c. injection at low-cell inocula, U9A cells induced tumors 75 times as large in vivo as did the K6 antisense transfectant. The decreases in in vitro invasion and anchorage-dependent colony formation seen in K6 cells were largely reversed by the addition of TGF beta1. Tumors that did arise from the K6 antisense transfectant cells had lost antisense TGF beta1 expression and expressed the same TGF beta1 mRNA levels as controls. U9A cells were more metastatic to the liver after intrasplenic injection than K6 cells. These findings demonstrate a role for autocrine TGE beta1 in colon cancer tumorigenicity and invasion. They also show that a relatively small decrease in TGF beta1 levels was enough to markedly decrease colon carcinoma cell aggressiveness. This is not unprecedented, as we had found in an earlier study that a small, 2-4-fold increase in TGF beta1 protein levels in human colon cancers correlated with disease progression to metastases (E. Friedman et al., Cancer Epidemiol, Biomarkers & Prev., 4:549-554, 1995).
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PMID:Transforming growth factor beta 1 (TGF beta 1) is an autocrine positive regulator of colon carcinoma U9 cells in vivo as shown by transfection of a TGF beta 1 antisense expression plasmid. 901 69

Our laboratory has developed two cellular models of human prostate cancer progression. The LNCaP prostate cancer progression model is based upon the well-known cellular interaction between human prostate or bone stromal cells and LNCaP cells in vivo. The marginally tumorigenic LNCaP cells acquired tumorigenic and metastatic potential upon cellular interaction with either prostate or bone fibroblasts. A subline termed C4-2 was observed to grow readily in castrated animals and acquired metastatic potential spreading from the primary tumor site to the lymph node, the seminal vesicles, and the axial skeleton, resulting in an intense osteoblastic reaction. The second model is ARCaP, where prostate cancer cells derived from the ascites fluid of a man with metastatic disease exhibited an Androgen- and estrogen-Repressed Prostate Cancer cell growth and tumor formation in either a hormone-deficient or a castrated environment. However, the growth of either the tumor cells in vitro or the tumors in vivo was suppressed by both estrogen and androgen. While the tumor cells expressed low levels of androgen receptor and prostate-specific antigen (PSA), they were highly metastatic when inoculated orthotopically. Distant metastases to a number of organs were detected, including the liver, lung, kidney, and bone. We have employed a human prostate cancer progression model as a system to study the efficacy of gene therapy. Results of the study show that whereas universal promoters, such as Cytomegalovirus (CMV) and Rous Sarcoma Virus (RSV) promoter-driven tumor suppressors (e.g. p53, p21, and p16), were effective in inhibiting prostate tumor growth, the advantages of driving the expression of therapeutic toxic genes using a tissue-specific promoter prostate-specific antigen (PSA) and a tumor--but not tissue-specific promoter, osteocalcin (OC), are preferred. In the case of the PSA promoter, we can achieve cell-kill in PSA-producing human prostate cancer cells. To circumvent the supporting role of bone stroma for prostate cancer epithelial growth, we have recently developed a novel concept where the expression of therapeutic toxic genes is driven by a tumor--but not a tissue-specific OC promoter. Osteocalcin-thymidine kinase (OC-TK) was found to efficiently eradicate the growth of osteosarcoma, prostate, and brain tumors both in vitro and in vivo. We observed that androgen-independent human prostate cancer cells lines expressed OC-TK at higher levels than androgen-dependent human prostate cancer cell lines. We have obtained data to suggest that Ad-OC-TK plus a pro-drug acyclovir (ACV) may be used as an effective therapy to treat prostate cancer bone metastasis in models where the growth of androgen-independent PC-3 and C4-2 tumors in the bone has occurred.
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PMID:Human prostate cancer progression models and therapeutic intervention. 943 28


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