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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Control of transformed cells by neighbouring normal cells is known since the beginning of transformation studies in vitro. The classical explanation for this phenomenon is based on proliferation inhibition of transformed cells by normal cells. We extend this model by presenting data that show that TGF-beta-treated normal cells can eliminate transformed cells by induction of apoptosis. Both the TGF-beta-induced signal pathway in normal cells, leading to the production of a short-lived apoptosis-inducing factor, as well as the specific interaction of this factor with transformed cells depend on the action of reactive oxygen species. Sensitivity to induction of apoptosis seems to be a common feature associated with the transformed state, independent of the originally transforming principle. Therefore, tumor development should require either interference with the process of elimination or acquisition of resistance against it. We discuss experimental evidence for interfering substances, such as antioxidants, as well as for genetic systems that protect transformed cells from the negative effects of their cellular environment, such as Bcl-2 or papilloma viruses. These findings, as well as the general resistance of exvivo tumor cells against induction of apoptosis are in line with the novel model of control of tumor progression presented by us in this review.
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PMID:Elimination of transformed cells by normal cells: a novel concept for the control of carcinogenesis. 872 Apr 67

Progress in prostate cancer research has been hindered by the lack of well characterized, immortalized, human prostatic epithelial cell lines that express markers of normal prostatic epithelial cells and mimic normal growth and differentiation responses to androgens. The objectives of this study were to: (i) establish immortalized cell lines from non-neoplastic, adult human prostatic epithelium using adenovirus-12/simian virus-40 (Ad12-SV40) hybrid virus; (ii) establish their prostatic epithelial origin; (iii) demonstrate androgen responsiveness; and (iv) examine response to growth factors. Primary epithelial cell cultures derived from a non-neoplastic, adult human prostate were infected with the Ad12-SV40 virus. Several immortalized clones were isolated. Single cell cloning of one clone, free of cytopathic effects, gave rise to the PWr-1E cell line. An immortalized cell line PWR-1E, which expresses many characteristics of normal prostatic epithelial cells was established. Immunostaining showed that cells express cytokeratins 8 and 18 normally expressed by differentiated, secretory prostatic epithelial cells. The most remarkable characteristics of PWR-1E cells are growth stimulation, increased expression of androgen receptor and induction of prostate specific antigen (PSA) expression in response to androgens, which indisputably establish their prostatic epithelial origin. They are positive for SV40 large-T antigen and show strong nuclear staining for p53. Cells from passages 23 and 40 were not tumorigenic in nude mice even when co-injected with Matrigel. They grow in a serum-free defined medium and respond to EGF, bFGF and TGF-beta. Passage 42-cells showed a human male (XY), hyperdiploid karyotype. The PWR-1E cell line is the only known Ad12-SV40-immortalized human prostatic epithelial cell line. PWR-1E cells can be used to study (i) the etiology and the multistep process of carcinogenesis and tumor progression in the human prostate; (ii) normal prostate physiology and differentiation; and (iii) potential prostate cancer chemopreventive agents.
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PMID:Prostate specific antigen and androgen receptor induction and characterization of an immortalized adult human prostatic epithelial cell line. 876 20

Tumor progression to the stage of metastasis may result in part from the selection of certain primary tumor cell clones which are phenotypically competent for survival, invasion, and growth at secondary sites. Selection for traits such as loss of growth inhibitory responses, acquisition of increased adhesiveness, increased local immunosuppression, and enhanced motility and collagenase activities likely contribute to cancer progression and may be regulated through the action of growth factors. The transforming growth factors (TGF-beta) family of growth factors has often been associated with these traits and tumor progression; therefore, elimination or subversion of TGF-beta-responsive pathways should be considered as a mechanistic framework for metastatic events. In this report, we have compared growth and extracellular matrix responses to TGF-beta in six metastatic and six primary tumor-derived cell lines in a mouse model of prostate cancer. We have found that tumor cell lines derived from focal pulmonary metastasis secreted relatively greater quantities of total TGF-betas, lost most or all TGF-beta1 growth inhibition, but responded to TGF-beta1 through induction of the type IV collagenase matrix metalloproteinase-9, whereas cell lines derived from tumors which proliferated at the primary site retained the growth inhibition but lacked collagenase activity. Synthesis of another extracellular matrix protein, plasminogen activator inhibitor 1, was stimulated by TGF-beta1 in both primary as well as metastatic tumors. These results suggest that acquisition of differential responses to the TGF-beta family could result in phenotypic traits which facilitate tumor metastasis from certain primary site clones.
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PMID:Transforming growth factor beta1 stimulates contrasting responses in metastatic versus primary mouse prostate cancer-derived cell lines in vitro. 876 34

TGF-beta s and their receptors are expressed ubiquitously, and they act as key regulators of many aspects of cell growth, differentiation, and function. Steroid action on target tissues is often associated with increase in TGF-beta isoforms. Regulation of TGF-beta expression and activation is crucial for normal development and growth control. The loss of responsiveness of different tumor cells to the antiproliferative effects of TGF-beta is a common feature in carcinogenesis. Multiple changes are required for the cells to gain complete resistance to TGF-beta growth inhibition (Fynan and Reiss, 1993; Kimchi et al., 1988; Samuel et al., 1992). Although many tumor cells are not growth inhibited by TGF-beta, they respond to TGF-beta treatment by changes in the expression of matrix components and enhanced proteolytic activity (KeskiOja et al., 1988). Agents that induce TGF-beta production in target tissues can have a chemopreventive or chemotherapeutic value for the management of epithelial malignancies. Conversely, data supporting a positive role for TGF-beta in established tumor progression are beginning to emerge (Arteaga et al., 1993a,b; Barrett-Lee et al., 1990; Arrick et al., 1992 ; E. A. Thompson et al., 1991). In later stages of tumor development, cell proliferation is often not inhibited by TGF-beta, and tumor cells secrete large amounts of this growth factor (Fynan and Reiss, 1993). In vivo TGF-beta secreted by tumor or stromal cells can influence host responses such as a natural killer cell function and thus indirctly support tumor cell viability (Arteaga et al., 1993b). TGF-beta may also affect tumor growth indirectly by stromal effects and promotion of angiogenesis. TGF-beta may also be involved in the progression of breast tumors from the steroid-sensitive to steroid-insensitive state (King et al., 1989). Understanding of the net effect of TGF-beta in different stages of tumor development is critical for the evaluation of its therapeutic value in cancer treatment.
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PMID:Transforming growth factor-beta system and its regulation by members of the steroid-thyroid hormone superfamily. 890 54

SPARC (secreted protein acidic and rich in cysteine) is an extracellular protein associated with tissues exhibiting high rates of cell proliferation and matrix remodeling. The current work shows that the human melanoma cell lines IIB-MEL-LES, IIB-MEL-IAN, and IIB-MEL-J and different human metastatic melanomas expressed high levels of SPARC mRNA and protein. By western blot analysis we detected a single secreted 42-kDa band in human diploid fibroblasts-conditioned medium and a 45- to 40-kDa doublet in the three melanoma cell lines and all the metastatic melanomas tested. Part of the melanoma samples and cell lines showed an additional doublet of 36-34 kDa. SPARC mRNA was expressed by the three established cell lines, 14 metastatic melanoma samples, and tumors raised in nude mice, and no spliced variants were found. The heterogeneous pattern of SPARC secreted by human melanoma cells is the result of post-translational glycosylation and a specific extracellular leupeptin-inhibitable cleavage. Unlike human fibroblasts, melanoma cells did not overexpress SPARC on addition of TGF-beta. Immunohistochemical analysis showed that SPARC was strongly expressed in 100% of primary melanomas (7 of 7) and metastatic melanomas (29 of 29), moderately expressed in most of the positive dysplastic nevi (13 of 14), and only weakly expressed in nevocellular nevi (4 of 25). Normal melanocytes did not express SPARC. The data suggest that the expression of SPARC is associated with the neoplastic progression of human melanoma.
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PMID:The expression of the secreted protein acidic and rich in cysteine (SPARC) is associated with the neoplastic progression of human melanoma. 900 36

The transforming growth factor (TGF)-beta1, TGF-beta2 and TGF-beta3 expressions were immunohistologically studied in tissues specimens from 120 patients with a pulmonary adenocarcinoma. The results of a univariate analysis indicated that the expression of each of the TGF-beta isoforms correlated with the prognosis. Of the three prognostic factors examined using Cox's stepwise regression model, the TGF-beta1 isoform was found to correlate with survival. These findings suggest that TGF-beta isoforms play an important role in tumor progression and that the TGF-beta1 isoform is a useful prognostic marker for pulmonary adenocarcinomas.
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PMID:Transforming growth factor-beta isoforms expressions in pulmonary adenocarcinomas as prognostic markers: an immunohistological study of one hundred and twenty patients. 907 83

This paper reviews the current advances in molecular genetics and biology of prostate cancer development. Many genetic alterations in prostate cancer have been identified. Some of these changes are early events and occur in prostatic intraepithelial neoplasia and primary cancer of prostate, some others occur in late stages of prostate cancer development. The significant genetic changes for prostate cancer include losses for chromosomes 8p, 5q, 13q, and so forth; gains for chromosomes 8q, 11p, 3q, and so forth; aneusomies of chromosomes 7 and 8; and allelic losses at chromosome regions 8p 12-21, 10q23-24, 16q22.1-24, and 7q31.1-31.2. The alteration of the p53 tumor-suppressor gene plays a role in a subset of advanced prostate cancer. Expressions of TGF-beta receptors, E-cadherin, C-CAM, KAI1, and some integrins have an inverse correlation with either prostatic carcinogenesis or progression of prostate cancer, or both. Protein expression of BCL-2 in prostate cancer is highly correlated with cancer progression and androgen-independent phenotype. More studies need to be performed to identify specific genes for those genetic alterations and to explore the clinical use of the known molecules in prostate cancer.
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PMID:Molecular advances in prostate cancer. 909 May 1

Induction of apoptosis in transformed fibroblasts by surrounding normal cells has been discussed as a potent early control step in carcinogenesis. According to this hypothesis, tumor progression should require resistance of transformed cells against this TGF-beta-triggered control mechanism. Here we show that Bcl-2, a protein involved in inhibition of apoptosis, can protect transformed cells from induction of apoptosis by surrounding cells. Rather than acting on the transformation process itself, Bcl-2 may thus represent an efficient modulator of carcinogenesis at an intercellular level.
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PMID:Interference of bcl-2 with intercellular control of carcinogenesis. 917 29

Transforming growth factor beta-1 (TGF-beta1) is a potent inhibitor of hepatocyte growth both in vivo and in vitro. In this study, we analyzed the effects of TGF-beta1 on both naturally occurring and diethylnitrosamine-induced hepatocarcinogenesis using single transgenic TGF-beta1 and double transgenic c-myc/TGF-beta1 mice in which the expression of both transgenes was targeted to the liver. Hepatocellular tumors developed spontaneously in 59% (10 of 17) of the TGF-beta1 mice by 16-18 months of age. Coexpression of TGF-beta1 and c-myc transgenes in the liver accelerated hepatic tumor growth in both the presence and absence of carcinogenic treatment. Moreover, diethylnitrosamine-initiated tumors in the c-myc/TGF-beta1 mice showed a high rate of malignant conversion associated with a reduced expression or lack of TGF-beta receptor type II. The results suggest that overexpression of TGF-beta1 may contribute to liver carcinogenesis and that loss of TGF-beta receptor type II transduced inhibitory growth signals and up-regulation of c-myc are critical steps in liver tumor progression.
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PMID:Constitutive expression of mature transforming growth factor beta1 in the liver accelerates hepatocarcinogenesis in transgenic mice. 918

We compared the cytogenetic pattern of 20 different primary tumor cell cultures (PTCC) of renal cell carcinoma (RCC) to their cytokine secretion and oncogene expression. High secretion of IL-6 (gene locus on chromosome 7p21-p14) was correlated with the gain of an additional chromosome 7. Structural changes involving chromosome 5q22, the site of the GM-CSF gene, were matched with the high secretion of GM-CSF in PTCC. No such association was found for beta 2-microglobulin, TGF-beta 1, TNF-alpha, IL-8, and oncogenes, such as c-fos, c-myc, and pan-ras. Our approach may be useful in simultaneously analyzing several factors contributing to tumor progression and may contribute to understanding the multistep development of RCC.
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PMID:Comparison of cytogenetics, cytokine secretion, and oncogene expression in primary cultures of renal carcinoma cells. 926 Jun 6


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