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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metastasis of colon carcinomas is assumed to be caused by multiple steps, which include a loss of cell adhesion that results in the release of carcinoma cells from the original tumor tissue. A human colon carcinoma cell line COKFu was established from a poorly differentiated metastatic adenocarcinoma without cell-cell adhesion and without expression of E-cadherin mRNA and protein. This cell line was co-transfected with mouse E-cadherin cDNA in an expression vector and a neomycin-resistant gene. The parental carcinoma cells had a spindle shape and were scattered, whereas the transfected cells, which expressed exogenous E-cadherin gene, showed a more compact shape with strong cell-cell adhesion and with increased adhesiveness to collagen gel. These cells showed a significantly low anchorage independency (2-7%) and decreased invasiveness (30%) compared to the parental cells. Growth rate of transfectants was decreased both in vitro and in the subcutis of nude mice, with decreased lymphnode metastasis in the case of intravenous injection. It was additionally found that activity of 62 kd gelatinase, secreted from parental cells, was lost or decreased in E-cadherin-transfected cells. These results suggest that E-cadherin is not only involved in the cell-cell adhesion of colon carcinomas, it also has a wider effect, including cell-substratum adhesion and the regulation of proteinase secretion from the cells, resulting in partial suppression of invasiveness and tumorigenic growth.
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PMID:Increased cell-substratum adhesion, and decreased gelatinase secretion and cell growth, induced by E-cadherin transfection of human colon carcinoma cells. 854 11

We investigated mutations of the epithelial (E)-cadherin gene and loss of heterozygosity (LOH) at flanking loci using three microsatellite markers on the long arm of chromosome 16 in 25 ductal carcinomas of the breast. Expression of E-cadherin was also investigated immunohistochemically. No mutations were detected in exons 6 through 9 of the E-cadherin gene. LOH was observed more frequently (42%) at D16S402 (16q-ter) than at D16S421 (16q22.3-q23.1) (17%), which is located near the E-cadherin gene. Expression of E-cadherin was observed at the cell borders in 92% (11/12) of the tumors examined. The absence of mutations in the E-cadherin gene and its conserved expression suggest that inactivation of E-cadherin does not contribute significantly to the invasion or metastatic potential of ductal carcinomas of the breast. Furthermore, the high frequency of LOH at 16q-ter suggests the existence of another tumor suppressor gene which may play a crucial role in the genesis of ductal carcinomas of the breast.
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PMID:Epithelial-cadherin gene is not mutated in ductal carcinomas of the breast. 856 96

E-cadherin (E-cad) is a calcium-dependent, epithelial cell adhesion molecule whose reduced or lost expression has been associated with tumor dedifferentiation and increased metastatic potential in human carcinomas. The authors studied immunohistochemically E-cad expression in frozen sections of 362 breast carcinomas using a monoclonal antibody (HECD-1). The immunohistochemical detection of reduced E-cad expression was confirmed by mRNA in situ hybridization with two different oligonucleotide probes. THe proportion of tumors with reduced or lost E-cad expression increased significantly from pure intraductal carcinomas (20%, 4 of 20) through invasive ductal (IDCs; 52%, 124 of 239) to recurrent carcinomas (64%, 18 of 28; chi square test for trend, P = .004). Invasive lobular carcinomas (ILCs) and IDCs differed from each other in their E-cad expression. None of the ILCs (n=55) retained normal E-cad expression in contrast to 48% (115 of 239) of the IDCs. In 259 primary IDCs, reduced E-cad expression was associated with high histologic grade (chi square test for trend, P < .001), negative estrogen receptor status (ER; Fisher's exact test; P = .042), and marginally with axillary node involvement (Fisher's exact test, P = .063). In a subset of 109 primary IDC patients whose clinical follow-up was available (median follow-up 51 months), reduced E-cad expression was associated with shortened disease-free survival (DFS; Mantel-Cox test, P = .027). In Cox's multivariate regression analysis, progesterone receptor status (P = .018) and E-cad expression (P = .072) were selected as independent predictors of DFS. Our findings provide clinical evidence that loss of normal E-cad expression is an indicator of increased invasiveness and dedifferentiation in breast carcinoma. E-cad is a potentially important prognostic factor in primary IDCs.
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PMID:Reduced E-cadherin expression is associated with invasiveness and unfavorable prognosis in breast cancer. 860 81

There is a need to establish animal models which are suitable for investigation of human gastric cancer metastasis to the liver. To this end, a human gastric carcinoma line, AZ521 was injected into the spleens of nude mice. Cells from the few liver metastatic foci of injected AZ521 were expanded "in vitro" and subsequently injected into the spleens of nude mice. By repeating these procedures three times, we were able to obtain a cell line, designated as AZ-H3c, with high metastatic potential in nude mice. Liver metastasis developed in 15 of 21 (71%) animals injected with AZ-H3c, but only in 14% of those injected with parental AZ521. Further, AZ-H3c caused faster tumor development than did AZ521. However, the primary AZ-H3c tumors and liver metastatic AZ-H3c tumors showed essentially the same histological appearance. We also analyzed the cell surface expression of adhesion molecules. The data showed that the expression of VLA-1, VLA-2, VLA-3, VLA-4, VLA-5 was enhanced in AZ-H3c. In contrast, the expression of VLA-6, (alpha(v)beta3), E-cadherin, ICAM-1 and LFA-1 was reduced in this high-metastatic line. These results suggest that (beta1) integrins play an important role in the liver metastasis of human gastric carcinoma cells. Our high-metastatic line should be useful for studies aimed at the prevention of liver metastasis.
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PMID:Establishment and characterization of human gastric carcinoma lines with high metastatic potential in the liver: changes in integrin expression associated with the ability to metastasize in the liver of nude mice. 860 64

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

Autocrine motility factor interacts with its cell surface receptor (AMF-R) to stimulate tumor cell motility. To study AMF-R expression following transformation of polarized epithelial MDCK cells, we have used the invasive Moloney sarcoma virus transformed MDCK (MSV-MDCK) cell population. Decreased E-cadherin expression of the transformed MSV-MDCK clones is associated with both increased cellular motility and increased AMF-R expression. Increased AMF-R expression is due to MSV transformation as differentially motile MSV-MDCK clones, which either retain low E-cadherin, exhibit equivalent high levels of AMF-R. Loss of the polarized epithelial phenotype and increased cellular motility following transformation of MDCK cells is thus associated with a shift from a high E-cadherin/low AMF-R to a low E-cadherin/low AMF-R phenotype.
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PMID:Inverse relation of autocrine motility factor receptor and E-cadherin expression following MDCK epithelial cell transformation. 861 93

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

Various types of tumors show aberrant expression and overexpression of epidermal growth factor (EGF) receptor and the degree of receptor expression correlates with a malignant phenotype in many epithelial tumors. However, in vitro evidence supporting the advantageous role of receptor overexpression is deficient. In this study, we compared the effects of exogenous EGF on the cell colony morphology in monolayer and collagen gel culture between HSC-1 squamous carcinoma cells overexpressing EGF receptor and their revertant subline cells. These cells formed coherent cell colonies under routine culture conditions, but addition of EGF induced dissociation of cell colonies within 24 h in the parent HSC-1 cells, though not in the subline cells. Since the colony dissociation apparently involved loss of cell-cell adhesion, we also studied the effects of EGF on E-cadherin expression and its function. Cell aggregation assays showed that EGF reduced E-cadherin function dose-dependently in the parent cells, but not in the subline cells. However, immunoblotting analysis and ELISA showed the absence of downregulation or degradation of E-cadherin. Instead, EGF tyrosine phosphorylated cadherin/catenin complex components including beta-catenin and increased the detergent solubility of E-cadherin in the parent cells. These results suggest that EGF modified the functional association between E-cadherin and actin filament through tyrosine phosphorylation of the cadherin/catenin complex and thereby made the adhesion molecule incompetent. Our results indicate that the ligand activation of overexpressed EGF receptor impairs E-cadherin-mediated cell-cell adhesion and causes dissociation of the squamous carcinoma cell colonies, which facilitates tumor cell invasion in vivo. This might be relevant to the advantageous role of EGF receptor overexpression in malignant phenotype of epithelial tumor cells.
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PMID:Ligand activation of overexpressed epidermal growth factor receptor results in colony dissociation and disturbed E-cadherin function in HSC-1 human cutaneous squamous carcinoma cells. 863 95

p120cas (CAS) is a protein tyrosine kinase substrate that associates directly with the cytoplasmic tail of the cell-cell adhesion molecule E-cadherin. CAS is thus part of a multimolecular complex that, along with other cadherin-binding proteins (catenins), mediates interactions between E-cadherin and the actin cytoskeleton. Down-regulation of E-cadherin expression and defects in catenin function have been implicated in tumor metastasis, but the role of CAS in these processes has not been addressed. Recently, the study of CAS was complicated when new anti-CAS antibodies revealed the presence of at least four putative CAS isoforms that appeared to vary in abundance between cell types. Here, we identify the four major isoforms expressed in murine fibroblasts, and we show that they are products of alternative splicing. Analysis of CAS isoforms in a variety of murine cell lines indicates that motile cells like fibroblasts and macrophages preferentially express CAS1 (i.e., CAS1A and CAS1B isoforms), and epithelial cells preferentially express CAS2 (i.e., CAS2A and CAS2B isoforms), whereas nonadherent cells (e.g., B cells, T cells, and myeloid cells) do not express detectable levels of CAS. Interestingly, CAS1 expression is dramatically up-regulated in a Src-transformed Madin-Darby canine kidney cell line, indicating that the pattern of isoform expression can be altered by cell transformation. Analysis of a variety of differentiated and metastatic human tumor cell lines reveals that CAS isoform expression in these cells is quite heterogeneous. Furthermore, several poorly differentiated cell lines fail to express particular isoforms that are typically observed in well-differentiated cell lines. These data raise the possibility that unbalanced expression of CAS isoforms in human carcinomas may influence cadherin function and contribute to malignant or metastatic cell phenotypes.
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PMID:Identification of murine p120 isoforms and heterogeneous expression of p120cas isoforms in human tumor cell lines. 865 9

The major obstacle towards improved survival from gastric cancer is in the development of metastatic disease. Techniques in cellular and molecular biology have now advanced to the point to allow an examination of specific biomolecules in processes related to gastric cancer cell invasion through the basement membrane of blood vessels or lymphatics (eg, the first step in developing metastatic disease). Identification of such biomolecules in primary gastric cancer has been enhanced by the establishment of primary human gastric cancer cell lines. These cell lines, named SK-GT for Sloan-Kettering gastric tumor, have provided the basis for a detailed analysis of the invasive phenotype of gastric cancer cells and has resulted in the identification of potentially important prognostic biomarkers. These molecular studies have revealed that in gastric cancer cells there exists a series of integrated biomolecules that are intimately involved in processes related to tumor cell invasion. Included among these are proteins associated with attachment to the basement membrane (ie, laminin receptor) as well as with proteolysis of the basement membrane (ie, matrix metalloproteinase-2, MMP-2). These factors, as well as others, have been clinically evaluated for their prognostic significance in patients with resected, primary gastric cancer. These clinical studies indicate that overexpression of factors associated with the invasion of gastric cancer cells through the basement membrane, including E-cadherin, MMP-2, plasminogen activator inhibitor-1 (PAI-1), and tissue inhibitor metalloproteinase-2 (TIMP-2), can be predictive of tumor recurrence and overall survival in patients with this disease.
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PMID:Invasion and metastases in gastric cancer: in vitro and in vivo models with clinical correlations. 865 15


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