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

The acquisition of invasive properties by transformed epithelial cells constitutes an essential step in the progression of carcinomas. We have defined 2 types of interferences leading to enhanced motility and invasiveness of epithelial cells: (i) disturbances of intercellular adhesion, and (ii) treatment with "scatter factor", a secretory protein of mesenchymal cells. Invasive properties (invasion of collagen gels or embryonal heart tissue) are acquired by epithelial cells in vitro when intercellular adhesion is inhibited by antibodies that are specific for the cell-cell adhesion molecule E-cadherin. Furthermore, we found that differentiated human carcinoma cell lines are noninvasive and express E-cadherin, whereas dedifferentiated carcinoma lines are invasive and have lost E-cadherin expression. Invasiveness of these latter cells could be prevented by transfection with E-cadherin cDNA and was again induced by treatment of the transfected cells with anti-E-cadherin antibodies. A correlation between the degree of tumor differentiation and the amount of E-cadherin expression was also visualized on frozen sections of ovarian carcinomas, lobular breast carcinomas, and squamous carcinomas of head and neck. Thus, loss of E-cadherin appears to be a critical step in the establishment of an invasive, i.e. fully malignant phenotype. Scatter factor, which is also capable of dissociating epithelial cell colonies in vitro, was isolated from conditional medium of human fibroblasts; it is a 92,000 mol.wt glycoprotein, which is proteolytically cleaved into 62,000 and 34/32,000 mol.wt subunits. The purified glycoprotein induces invasion of MDCK cells into collagen matrices, and induces or enhances the invasive properties of various human carcinoma cell lines. Sequencing of tryptic peptides of scatter factor revealed strong similarity with hepatocyte growth factor. Furthermore, both factors exhibit identical activities, i.e. scatter factor stimulates DNA synthesis of primary hepatocytes and hepatocyte growth factor dissociates and increases the motility of various epithelial cells. Thus scatter factor and hepatocyte growth factor represent identical or closely similar proteins.
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PMID:The role of E-cadherin and scatter factor in tumor invasion and cell motility. 183 25

The past year has been the discovery and further analysis of several genes and protein products that are critically involved in the generation of invasive and metastatic tumor cells. Like oncogenes and tumor suppressor genes, the genes responsible for invasive and metastatic phenotypes can function in a dominant or recessive fashion. In this review, particular emphasis will be given to the dominantly acting genes encoding the cell adhesion molecule CD44 and the motility factor scatter factor, and the recessively acting genes encoding the cell adhesion molecule E-cadherin and nm23.
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PMID:Dominant and recessive genes involved in tumor cell invasion. 193 Oct 83

Tissue sections of 32 squamous cell carcinomas (SCCs) of the head and neck were investigated for the expression of the epithelium-specific cell adhesion molecule E-cadherin. We found that E-cadherin expression is inversely correlated both with the loss of differentiation of the tumor and with lymph node metastasis. The well-differentiated SCCs expressed E-cadherin, often as strongly as the normal stratified epithelium (12 cases were tested); the moderately differentiated SCCs expressed intermediate amounts of E-cadherin or were heterogeneous (15 cases were analyzed); whereas the poorly differentiated SCCs were all E-cadherin-negative (five cases were investigated). Furthermore, seven of eight infiltrated lymph nodes of SCCs were E-cadherin-negative. These data indicate that the loss of the cell adhesion molecule E-cadherin in fact plays an important role in the progression of human squamous cell carcinomas, i.e., that down-regulation of expression is associated with dedifferentiation and metastasis of the tumor cells in vivo.
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PMID:E-cadherin expression in squamous cell carcinomas of head and neck: inverse correlation with tumor dedifferentiation and lymph node metastasis. 193 95

We have previously produced a monoclonal antibody (MAb) against TMK-1 cells, a poorly differentiated stomach-cancer cell line, and designated the antigen as 9A3. Immunohistochemical analysis of various tumor tissues revealed that the expression of 9A3 antigen is specific for human adenocarcinoma. In the present study, we analyzed the expression patterns of 9A3 antigen on TMK-1 cells and compared them with the expression patterns of E-cadherin and epidermal-growth-factor (EGF) receptors, using immunofluorescent microscopy and flow cytometry. The flow cytometric analysis revealed that the TMK-1 cell population consists of 9A3-positive cells and 9A3-negative cells. The isolated 9A3-negative cell population generates 9A3-positive cells as they divide, whereas the isolated 9A3-positive cell population does not generate 9A3-negative cells. The 9A3-positive cells grow as tight colonies, whereas the 9A3-negative cell form loose colonies in soft agar culture. E-cadherin was expressed only in the 9A3-positive TMK-1 cells and not in the 9A3-negative cells. In contrast, EGF receptor was expressed in both cell populations. The 9A3 antigen was localized mainly at the cell-cell adhesion sites where E-cadherin was apparently condensed.
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PMID:Flow cytometric analysis of the expression of 9A3 antigen, E-cadherin and EGF receptor in TMK-1 stomach cancer cells. 201 60

Human fetal development depends on the embryo rapidly gaining access to the maternal circulation. The trophoblast cells that form the fetal portion of the human placenta have solved this problem by transiently exhibiting certain tumor-like properties. Thus, during early pregnancy fetal cytotrophoblast cells invade the uterus and its arterial network. This process peaks during the twelfth week of pregnancy and declines rapidly thereafter, suggesting that the highly specialized, invasive behavior of the cytotrophoblast cells is closely regulated. Since little is known about the actual mechanisms involved, we developed an isolation procedure for cytotrophoblasts from placentas of different gestational ages to study their adhesive and invasive properties in vitro. Cytotrophoblasts isolated from first, second, and third trimester human placentas were plated on the basement membrane-like extracellular matrix produced by the PF HR9 teratocarcinoma cell line. Cells from all trimesters expressed the calcium-dependent cell adhesion molecule cell-CAM 120/80 (E-cadherin) which, in the placenta, is specific for cytotrophoblasts. However, only the first trimester cytotrophoblast cells degraded the matrices on which they were cultured, leaving large gaps in the basement membrane substrates and releasing low molecular mass 3H-labeled matrix components into the medium. No similar degradative activity was observed when second or third trimester cytotrophoblast cells, first trimester human placental fibroblasts, or the human choriocarcinoma cell lines BeWo and JAR were cultured on radiolabeled matrices. To begin to understand the biochemical basis of this degradative behavior, the substrate gel technique was used to analyze the cell-associated and secreted proteinase activities expressed by early, mid, and late gestation cytotrophoblasts. Several gelatin-degrading proteinases were uniquely expressed by early gestation, invasive cytotrophoblasts, and all these activities could be abolished by inhibitors of metalloproteinases. By early second trimester, the time when cytotrophoblast invasion rapidly diminishes in vivo, the proteinase pattern of the cytotrophoblasts was identical to that of term, noninvasive cells. These results are the first evidence suggesting that specialized, temporally regulated metalloproteinases are involved in trophoblast invasion of the uterus. Since the cytotrophoblasts from first trimester and later gestation placentas maintain for several days the temporally regulated degradative behavior displayed in vivo, the short-term cytotrophoblast outgrowth culture system described here should be useful in studying some of the early events in human placen
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PMID:Adhesive and degradative properties of human placental cytotrophoblast cells in vitro. 247 56

E-Cadherin is a member of the cadherin family, which plays a key role in intercellular adhesion in various tumors as well as in normal tissues. Here, we examined the expression of this adhesion molecule in a murine ovarian tumor line OV2944, whose sublines show different degrees of spontaneous metastasis from subcutaneous sites; sublines LM-1 and LM-3 exhibit a low metastatic activity but a variant subline HM-1 has a high metastatic activity. When the expression of E-cadherin in these cells was examined by immunoblot analysis, the highly metastatic HM-1 cells was found to express an extremely small amount of this molecule, as compared with a high level of E-cadherin expression in the weakly metastatic LM-1 and LM-3 cells. Northern blot analysis showed that the amount of tanscripts from the E-cadherin gene is proportional to the amount of proteins detected in these cells. Immunofluorescence staining revealed that cells of the highly metastatic line were heterogeneous, that is, their cultures contained both E-cadherin-positive and negative cells. In contrast, cells of the weakly metastatic lines homogeneously expressed E-cadherin. When the highly metastatic line was subcloned, all the subclones consisted of E-cadherin-positive and negative cells. These results suggest that the expression of E-cadherin gene is not stably controlled in the highly metastatic line.
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PMID:Unstable expression of E-cadherin adhesion molecules in metastatic ovarian tumor cells. 250 22

The invasion-suppressor molecule E-cadherin mediates Ca(2+)-dependent cell aggregation and prevents invasion. E-cadherin-positive Madin-Darby canine kidney (MDCK) cells that were non-invasive in vitro formed, upon i.p. injection, tumors that were invasive. Differentiated tubular tumor areas showed an intense immuno-signal for E-cadherin at intercellular contacts, whereas undifferentiated structures did not. Cell lines derived from such tumors turned out to be invasive in vitro and showed decreased Ca(2+)-dependent cell aggregation but no change in E-cadherin immunopositivity. This combination of phenotypes indicated a loss of the E-cadherin invasion-suppressor function. Micro-encapsulation of i.p.-injected cells prevented the loss of the E-cadherin invasion-suppressor function. We concluded that this loss in vivo was dependent upon immediate contacts between tumor cells and host cells or upon host factors that could not cross the capsule membrane.
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PMID:Micro-encapsulation of MDCK-ras-e cells prevents loss of E-cadherin invasion-suppressor function in vivo. 751 77

Since one crucial step in tumor progression consists of the acquisition of invasive and metastatic properties, it is important to analyze the mechanisms used by cancer cells to disperse. Among the possible mechanisms of cell dispersion, cell motility appears as a central phenomenon that still needs to be understood at the molecular level. Our experimental approach to the contribution of cell motility in carcinoma cell dissemination is based on the study of the NBT-II rat bladder carcinoma cell line. The epithelial cell line gives rise to isolated, actively migrating, fibroblast-like cells in response to specific stimuli (collagens and acidic fibroblast growth factor [aFGF]). Analysis of the scattering response indicates that the different stimuli can synergize, leading to increased motility and invasiveness. NBT-II cells have two types of response to aFGF: they can either proliferate or scatter. In addition, the two responses are mutually exclusive, suggesting that the cell status can dictate whether or not tumor cells will disperse after exposure to a scatter factor. Finally, recent studies on the involvement of epithelial-specific cadherins in the process of aFGF-induced cell scattering indicate that a sustained expression of E-cadherin is not sufficient to protect cells from dispersing. In conclusion, our experimental model offers the opportunity to dissect the molecular events leading to tumor cell dissemination.
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PMID:Involvement of cell motility in tumor progression. 751 90

Decreased levels of the cell-cell adhesion molecule E-cadherin are associated with loss of differentiation in a number of human carcinomas. However, the value of E-cadherin as a prognostic marker in these cancers is largely undetermined. A previous study of E-cadherin levels in prostate cancer revealed that almost 50% of tumors examined had reduced or absent levels of this protein (Umbas et al., Cancer Res., 52: 5104-5109, 1992). To determine the potential prognostic significance of this finding, prostate cancer specimens from 89 patients were evaluated immunohistochemically for E-cadherin expression, and the results were related to histopathological grade, tumor stage, presence of metastases, and survival. As previously observed, a significant inverse correlation was found between E-cadherin expression and tumor grade. Importantly, we also found significant correlations between E-cadherin expression and tumor stage and overall survival. Sixty-three percent of the tumors that extended beyond the prostate capsule (T3-4) versus 33% of the tumors confined to the prostate (T1-2) had aberrant expression (chi 2 = 8.1, P < 0.005). Seventy-six percent of the primary tumors from patients that presented with metastases showed aberrant staining compared to 32% from patients without metastases (chi 2 = 14.9; P < 0.001). The life table analysis showed a significantly higher survival rate for patients with normal staining compared to patients with aberrant expression (chi 2 = 20.4, P < 0.001 by log rank test). Moreover, abnormal expression of E-cadherin correlated significantly with progression after radical prostatectomy (P < 0.005). These results suggest that E-cadherin expression can serve as a prognostic indicator for the biological potential of prostate cancer.
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PMID:Decreased E-cadherin expression is associated with poor prognosis in patients with prostate cancer. 751 46

Advanced ovarian cancers contain 2 distinct phenotypic populations: (a) free-floating tumor cells in the ascitic fluid and (b) solid tumors. Ascites cells are derived from the solid tumors and spread throughout the peritoneum. Changes in cell-cell and cell-extracellular matrix interactions are thought to be responsible for the origin of ascites cells. Since E-cadherin molecules play a crucial role in the cell-cell interactions in epithelial cells, we investigated the expression of E-cadherin in these 2 phenotypic populations. Paired samples of ascites and solid tumors were obtained from patients. Both primary tumors and tumor cells isolated from an experimental model showed a marked decrease in E-cadherin expression in the ascites cells compared to the respective solid tumors. Semi-quantitative, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine the steady-state levels of E-cadherin-specific mRNA. Results indicate that the primary tumors had significantly lower levels of E-cadherin transcript in ascites cells when compared to their solid tumor counterparts. Changes in E-cadherin expression were also reflected in the invasion capacity of tumor cells in vitro. Ascites cells were 4-fold more invasive then solid tumor cells, suggesting that ascites cells are a highly malignant phenotype.
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PMID:Differential expression of the cell-cell adhesion molecule E-cadherin in ascites and solid human ovarian tumor cells. 751 85


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