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

To investigate the cellular mechanisms of ovarian epithelial carcinogenesis, a series of progressively transformed rat ovarian surface epithelial (ROSE) cell lines were developed and studied. Transfection of primary ROSE cells and an immortalized ROSE line (ROSE 199) with the pSV3neo plasmid (SV40 T-antigen) yielded transformed lines which retained epithelial morphology. In vivo selection of these pSV3neo cell populations resulted in further phenotypic transformation. Transfection of ROSE 199 with pSV2neo/c-H-rasEJ (rasEJp21) resulted in a malignant line which appeared fibroblast-like and formed invasive sarcomas both in athymic mice and in immunocompetent rats. Gap junctional intercellular communication (GJIC) and cell-cell adhesion were studied in this series of ROSE lines. Both c-H-rasEJ-transformation and in vivo selection resulted in a significant reduction of GJIC between adjoining cells and a transition of in vitro migration as continuous epithelial sheets to the dissociation of individual cells. This apparent shift in cell adhesiveness was associated with reduced expression of the E-cadherin adhesion molecule. Our data suggest that neoplastic progression of the ovarian surface epithelium may be associated with concomitant reductions in GJIC, E-cadherin expression and functional adhesiveness.
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PMID:An in vitro model of ovarian epithelial carcinogenesis: changes in cell-cell communication and adhesion occurring during neoplastic progression. 832 8

In many human colorectal cancers, the DCC gene encoding for a homologue of the neural cell adhesion molecule (N-CAM) is found to be deleted. Previous work suggested that gap junctional intercellular communication (GJIC) might play an important role in carcinogenesis and could be regulated by the expression of cell adhesion molecules such as E-cadherin in some epithelial cell systems. In order to examine whether the deletion of the putative cell adhesion molecule DCC is related to the level of GJIC, which might, in turn, be important in human colorectal cancers, we compared levels of expression of the DCC gene with the GJIC capacity of a panel of human colorectal adenocarcinoma cell lines isolated from different stages of tumor progression. While the level of GJIC varied between the cell lines studied, we found no correlation between their communication capacity and DCC expression revealed by a reverse-transcriptase/polymerase chain reaction method. This lack of correlation suggests that DCC is not a crucial regulator of GJIC.
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PMID:Lack of correlation between the gap junctional communication capacity of human colon cancer cell lines and expression of the DCC gene, a homologue of a cell adhesion molecule (N-CAM). 839 66

Loss or decreased expression of E-cadherin (ECD), which forms an epithelial junction complex that includes several other proteins and triggers signal transduction, may contribute to tumor progression. In the present study, we examined 90 transitional cell cancers (TCCs), 47 urinary bladder cancers and 43 ureteral or renal pelvic cancers, as well as TCC and papilloma cell lines to determine whether they express ECD. We classified ECD expression into normo-expression (like normal epithelial), decreased and loss of ECD staining on TCCs (urinary bladder, renal pelvic or ureteral). We found that low-stage TCCs expressed normal ECD in 68%, decreased of ECD in 20% and loss of ECD in 12%, whereas high-stage TCCs expressed 29%, 41% and 30% of ECD staining, respectively (P < 0.01). Furthermore, grade 1 TCCs were all estimated to show normo-expression, grade 2 TCCS expressed normal ECD in 49%, decreased of ECD in 41% and loss of ECD in 10% grade 3 TCCs classified as 20%, 30% and 50%, respectively (P < 0.01). Staining for cultured cell lines showed positive membranous staining for ECD in a benign papilloma cell line, RT4 and a TCC cell line, HT1376, but not in a TCC cell line, T24. Reverse-transcription polymerase chain reaction showed the presence of ECD and alpha-catenin mRNA in RT4 and HT1376, and only alpha-catenin in T24. Thus, it is more likely that decrease or loss of ECD might contribute to the malignant character of tumor cells and result in tumor progression.
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PMID:Loss of human E-cadherin (ECD) correlated with invasiveness of transitional cell cancer in the renal pelvis, ureter and urinary bladder. 861 3

This study is a comparative analysis of the prevalence, absolute number and aggregation status of bone marrow micro-metastases (BMM) between breast (n=234) and gastric (n=102) cancer patients based on a standardized number of 1 X 10(6) bone marrow-derived cells per patient. Additionally, expression of the epithelial cell adhesion molecule E-cadherin was analyzed on disseminated tumor cells. A positive BMM status was demonstrated in 88/234 breast and 45/102 gastric cancer patients. The presence of CK18+ cells positively correlated with parameters of advanced tumor progression in breast, but not in gastric cancer. Interestingly, 25.2% of the node-negative patients already had micrometastatic cells in the bone marrow at diagnosis. Regarding the absolute number of CK18+ cells and the frequency of CK18+ cell clusters, no significant difference was found between the 2 tumor types. However, clusters consisting of more than 10 CK18+ cells (type II clusters) were present exclusively in breast cancer patients. Additionally, co-expression of CK18 and E-cadherin was detectable in 15/21 micrometastases-positive breast but in only 1/9 gastric cancer patients. While prevalence of micrometastatic cells in bone marrow is discussed as an early indicator for systemic disease, aggregation status and a certain antigen profile might be indicative for site-specific differences in the manifestation pattern of solid metastases.
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PMID:Comparative analyses of bone marrow micrometastases in breast and gastric cancer. 863 87

We studied the adhesive characteristics of melanocytes, cultured either in the presence of the mitogen phorbol 12-myristate 13-acetate (PMA) that keeps them in a proliferative state, or in the absence of PMA allowing them to differentiate. On proliferating melanocytes, several integrins, ICAM-1, E-cadherin, and CD44 were expressed. In the absence of PMA, proliferation was arrested, melanin synthesis increased, and the morphology of the melanocytes became more spreaded. Under these conditions, expression of integrins alpha 3 beta 1 and alpha 5 beta 1 decreased, whereas expression of alpha 2 beta 1, alpha 4 beta 1, and alpha 6 beta 1 increased. No changes were observed for any of the other adhesion molecules. Immunoprecipitations from metabolically labeled cells confirmed the shift in integrin expression at the level of biosynthesis. The increased surface expression of alpha 2 beta 1 and alpha 6 beta 1 in the absence of PMA was accompanied by an induction of adhesion to basement membrane components collagen and laminin through these integrins. Integrin alpha 5 beta 1/alpha v beta 3-mediated adhesion to fibronectin, CD44-mediated adhesion to hyaluronate, and E-cadherin/beta 1-integrin-mediated adhesion to keratinocytes were not affected by PMA. These findings indicate that by selective modulation of the expression of adhesion molecules, adhesion to components of the basement membrane is reduced in proliferating melanocytes, whereas adhesion to keratinocytes is maintained. Similar events may be involved in melanocyte proliferation and migration during wound healing and initial steps of melanocytic tumor progression.
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PMID:Loss of adhesion to basement membrane components but not to keratinocytes in proliferating melanocytes. 873 21

Recent molecular biology investigations have demonstrated that tumor progression and dissemination in bladder cancer is a highly complicated phenomenon, consisting of multiple distinct steps and regulated by a great number of different genes. Some of these genes involved in the specific steps of tumor progression and dissemination have been identified. Several oncogenes, e.g., the epithelial growth factor receptor (EGF-R), and tumor-suppressor genes, e.g., the p53 gene, have been found to correlate significantly with tumor progression. The decreased expression of cell-adhesion molecules such as E-cadherin appears to facilitate tumor-cell detachment in the primary tumor, whereas expression of the intercellular adhesion molecule (ICAM)-1 might be of relevance for cell attachment at the metastatic site. Tumor invasion through the basement membrane has been correlated with a decreased expression of laminin and elevated urinary levels of acidic fibroblast growth factor. Although the complex processes related to dissemination are far from being completely understood, the finding of differential expression of distinct genes appears to provide the first targets for therapeutic intervention.
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PMID:Molecular biology of dissemination in bladder cancer--laboratory findings and clinical significance. 880 98

Aberrant glycosylation expressed in glycosphingolipids and glycoproteins in tumor cells has been implicated as an essential mechanism in defining stage, direction, and fate of tumor progression. This general concept is supported by results from three lines of study: (a) Numerous clinicopathological studies have shown a clear correlation between aberrant glycosylation status of primary tumor and invasive/metastatic potential of human cancer as reflected by 5- or 10-year survival rates of patients. (b) Carbohydrates expressed in tumor cells are either adhesion molecules per se or modulate adhesion receptor function. Some are directly involved in cell adhesion. They are recognized by selectins or other carbohydrate-binding proteins or by complementary carbohydrates (through carbohydrate-carbohydrate interaction). N- or O-glycosylation of functionally important membrane components may alter tumor cell adhesion or motility in a direction that either promotes or inhibits invasion and metastasis. Examples of such receptors are E-cadherin, integrins, immunoglobulin family receptors (e.g., CD44), and lysosome-associated membrane protein. (c) Gangliosides and sphingolipids modulate transmembrane signaling essential for tumor cell growth, invasion, and metastasis. The transducer molecules susceptible to gangliosides and sphingolipids include integrin receptors, tyrosine kinase-linked growth factor receptors, protein kinase C, and G-protein-linked receptor affecting protein kinase A. Some glycosphingolipids (e.g., Gb3Cer, Le(y), ceramide, and sphingosine induce tumor cell differentiation and subsequent apoptosis. Shedded gangliosides may block immunogenicity of tumor cells, providing conditions favorable for "escape" from immunological suppression of tumor growth by the host. Various reagents that block carbohydrate-mediated tumor cell adhesion or block glycosylation processing have been shown to inhibit tumor cell metastasis. This provides the basis for further development of "anti-adhesion therapy." Ganglioside analogues and sphingolipid analogues that inhibit protein kinase C and receptor-associated tyrosine kinase have been applied for inhibition of metastasis. A crucial mechanism for inhibition of metastasis by these reagents may involve blocking of transmembrane signaling for expression of P- and E-selectin. This provides the basis for development of "ortho-signaling therapy."
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PMID:Tumor malignancy defined by aberrant glycosylation and sphingo(glyco)lipid metabolism. 896 75

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

Epithelial cells are the most important cell type in the development of human malignancies. More than 90% of all malignant tumors are carcinomas, and thus of epithelial origin. Aberrant growth and the ability to invade the underlying tissues are intrinsic properties of the fatally altered cells. Multiple genetic alterations that can influence growth and genetic stability of the carcinoma cells have been characterised during tumor progression. Loss of epithelial morphology and the acquisition of mesenchymal characteristics are typical for carcinoma cells late in tumor progression and correlate with metastatic potential. In vitro, epithelial-mesenchymal transitions can be induced by interference with the integrity of the adherens junction, by signalling via tyrosine kinases, and by oncogene expression. In carcinoma cells, loss or downregulation of E-cadherin expression are frequently observed in carcinomas, and correlate with the malignancy of the tumor. In general, this change in expression is regulated at the transcriptional level. However, tumor types or cell lines exist which show mesenchymal characteristics but nevertheless express E-cadherin protein or mRNA. A more-detailed analysis demonstrated that other mechanisms that interfere with E-cadherin-mediated cell adhesion can be operative. Mutations in the E-cadherin gene and loss or mutation of the second, intact copy as well as mutation in the catenin genes, which encode proteins that interact with the cytoplasmic portion of E-cadherin, can be observed. In addition, transient or unregulated phosphorylation by receptor tyrosine kinases or oncogenic tyrosine kinases, respectively, can interfere with the epithelial morphology and induce a mesenchymal conversion. Since tyrosine phosphorylation of beta-catenin correlates with the epithelial-mesenchymal transition that is observed, E-cadherin-mediated cell adhesion might be modulated by such a mechanism. Interestingly, the same molecules implicated in the control of malignant properties turn out to play fundamental roles in the control of normal epithelial growth, differentiation and morphogenesis.
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PMID:Epithelial-mesenchymal transitions in cancer progression. 912 38

Signaling via intercellular junctions plays an important role in the regulation of growth and differentiation of epithelial cells. Loss of cell-cell contacts has been implicated in carcinogenesis, tumor progression, and metastasis. Here, we investigated whether 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] was able to stimulate the assembly of adherens junctions and/or desmosomes in cultured human keratinocytes. After 4-day incubation, 1,25-(OH)2D3 caused assembly of adherens junctions, but not desmosomes. The adherens junctions were identified upon known ultrastructural criteria and evidence of the translocation of specific junctional proteins (E-cadherin, P-cadherin, alpha-catenin, and vinculin) to the cell-cell borders. The presence of alpha-catenin and vinculin at cell-cell borders indicated that the adherens junctions were functional. This was further supported by showing that anti E-cadherin antibody inhibited the 1,25-(OH)2D3-induced keratinocyte stratification. A relation between protein kinase C and adherens junction regulation was noticed. 1,25-(OH)2D3-dependent formation of junctions was blocked by the inhibitors of protein kinase C, bisindolylmaleimide and 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H-7), and treatment of keratinocytes with 1,25-(OH)2D3 caused a rapid activation of protein kinase C and its translocation to the membranes. Formation of intercellular contacts may be an important mechanism of 1,25-(OH)2D3 action in hyperproliferative and neoplastic diseases.
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PMID:1,25-dihydroxyvitamin D3 stimulates the assembly of adherens junctions in keratinocytes: involvement of protein kinase C. 916 7


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