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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer metastasis poses the greatest challenge to the eradication of malignancy. The majority of clinical and experimental evidence indicates that metastasis is a non-random, organ-specific process. Tumor cell interaction with endothelium and subendothelial matrix constitutes the most crucial factor in determining the organ preference of metastasis. A plethora of cell surface adhesion molecules, which encompass four major families (i.e., integrins, cadherins, immunoglobulins and selectins) and many other unclassified molecules, mediate tumor-host interactions. Adhesion molecules and adhesion processes are involved in most, if not all, of the intermediate steps of the metastatic cascade. Decreased E-cadherin expression and increased CD44 expression are clearly correlated with the acquisition of the invasive capacity of primary tumor cells. Similarly, altered expression pattern of many other adhesion molecules such as upregulated expression of the laminin receptors and depressed expression of fibronectin receptors (alpha 5 beta 1) appears to be involved in tumor cell invasion into the subendothelial matrix. Tumor cell-endothelium interactions involve several well-defined sequential steps that can be analyzed by the 'Docking and Locking' hypothesis at the molecular level. Tumor cell-matrix interactions are determined by the repertoire of adhesion receptors of tumor cells and the unique composition of organ-specific matrices. Our experimental data, together with others', suggest that the integrin alpha IIb beta 3 is one of the major players in these tumor-host interactions. Tumor-host interaction is a dynamic process which is constantly modulated by a host of factors including various cytokines, growth factors and arachidonate metabolites such as 12(S)-HETE. Delineation of the molecular mechanisms of tumor-host interactions may provide additional means to intervene in the metastatic process.
Cancer Metastasis Rev 1992 Nov
PMID:Adhesion molecules and tumor cell interaction with endothelium and subendothelial matrix. 142 22

Cadherins represent a family of Ca(2+)-dependent cell adhesion molecules involved in homotypic, homophilic cell-cell interactions. Recent studies have shown that the cadherins can play a role in invasive and metastatic behavior. Using the established Dunning R-3327 model system of serially transplantable rat prostate cancers, the expression of E- and P-cadherin in rat prostatic cancer was studied. Analysis within this system demonstrated that whereas E-cadherin was expressed in the normal rat prostate and the well- or moderately differentiated, noninvasive Dunning tumors, no expression, either at the mRNA or at the protein level, could be detected in the invasive sublines. Since not all invasive Dunning tumors studied have metastatic ability, these results suggest that a decreased expression of E-cadherin is correlated with invasive behavior rather than with metastatic ability. Recently, genetic instability occurred in an animal bearing the well differentiated, androgen-responsive, slow growing, nonmetastatic Dunning R-3327-H rat prostate cancer resulting in the progression to an anaplastic, androgen-independent, fast growing, highly metastatic state. This spontaneously arising tumor, termed the AT6 subline, in its original host was heterogeneously composed of both a well differentiated and an anaplastic population of cancer cells in which areas of squamous cell differentiation were occasionally observed. The original animal bearing this heterogeneous AT6 cancer developed multiple metastases, the lung metastases being heterogeneously composed of anaplastic and squamous cell populations. Cytogenetic analysis demonstrated that the lung metastases were derived from a specific subpopulation of cancer cells present in the original AT6 primary tumor. Immunohistochemical studies demonstrated that only the area of lung metastases displaying squamous morphology were positive for E-cadherin. In contrast, the anaplastic areas of the lung metastases and the metastases in other organs were E-cadherin negative. By the first passage of the AT6 tumor only the anaplastic cells were present and no detectable E-cadherin mRNA or protein was found in the primary tumor and metastatic deposits. These results suggest that a decreased expression of E-cadherin is associated with the progression of prostatic cancer.
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PMID:Decreased expression of E-cadherin in the progression of rat prostatic cancer. 158 9

The ability of carcinomas to invade and to metastasize largely depends on the degree of epithelial differentiation within the tumors, i.e., poorly differentiated being more invasive than well-differentiated carcinomas. Here we confirmed this correlation by examining various human cell lines derived from bladder, breast, lung, and pancreas carcinomas. We found that carcinoma cell lines with an epithelioid phenotype were noninvasive and expressed the epithelium-specific cell-cell adhesion molecule E-cadherin (also known as Arc-1, uvomorulin, and cell-CAM 120/80), as visualized by immunofluorescence microscopy and by Western and Northern blotting, whereas carcinoma cell lines with a fibroblastoid phenotype were invasive and had 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 mAbs. These findings indicate that the selective loss of E-cadherin expression can generate dedifferentiation and invasiveness of human carcinoma cells, and they suggest further that E-cadherin acts as an invasion suppressor.
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PMID:E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. 200 22

The 120-kDa cell-cell adhesion molecule E-cadherin is localized at the epithelial junctional complex and participates in the organization and maintenance of epithelia. The Madin Darby canine kidney (MDCK) cell line expresses E-cadherin in a stable way and forms polarized epitheloid structures in vitro. Harvey-murine-sarcoma-virus-transformed derivatives (MDCK-ras) produce malignant (i.e., invasive and metastatic) tumors in nude mice. We obtained evidence that E-cadherin is down-regulated in nude mouse tumors and that this down-regulation is reversible. MDCK-ras-e cell lines were cloned in vitro from MDCK-ras cell cultures. They showed an epithelioid morphotype and expressed E-cadherin at homogeneously high level. This characteristic has been conserved for at least 60 passages in vitro. MDCK-ras-e cells were not invasive in vitro. When injected into nude mice, however, they produced invasive and metastatic tumors. Primary tumors as well as large metastases were heterogeneous, showing E-cadherin-positive well differentiated epithelial structures and E-cadherin-negative undifferentiated areas. Metastasis-derived cell cultures contained both E-cadherin-positive and E-cadherin-negative MDCK-ras-e cells during early passages in vitro. During further culture, however, they regained the homogeneous E-cadherin-positive characteristic of the original MDCK-ras-e cell line. The behavior of MDCK-ras-e cells in vitro, as compared with its in vivo behavior, points to the existence of host factors which are able to down-regulate E-cadherin expression. We hypothesize that this down-regulation plays a basic role in invasion.
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PMID:Down-regulation of E-cadherin expression in Madin Darby canine kidney (MDCK) cells inside tumors of nude mice. 201 Feb 35

Fifty-two lung carcinomas obtained at surgical resection were examined by immunofluorescence for their expression levels and patterns of the calcium-dependent intercellular adhesion molecule E-cadherin. In well-differentiated squamous cell and adenocarcinomas expression of E-cadherin was confined to the lateral cell border, similar to the expression level and pattern of normal lung tissue. The E-cadherin level was reduced and the expression pattern was spotty or diffuse in moderately and poorly differentiated squamous cell carcinomas and in small cell carcinomas of the lung. Also, most metastases resected had a reduced level and an altered pattern of E-cadherin expression. In contrast, no such correlation was found in adenocarcinomas of the lung. This indicates that different cellular mechanisms are responsible in the progression of squamous cell carcinomas versus adenocarcinomas of the lung.
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PMID:Differences of E-cadherin expression levels and patterns in human lung cancer. 751 35

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

We compared tumor grade and DNA content with expression of E-cadherin (E-CD), a cell adhesion molecule associated with cell-cell and cell-matrix interaction, leukocyte function, and tumor invasion and metastases, on 56 prostate carcinoma needle biopsies. The findings were correlated with final pathologic stage at subsequent prostatectomy, preoperative serum prostate-specific antigen level and further development of metastases during an initial 2.4-yr mean clinical follow-up period (range 0.5 to 5.5 yr). E-CD expression (uvomorulin, L-CAM, cell CAM 80/120, ARC-1, Sigma, St. Louis, MO) was measured by double-linked immunoalkaline phosphatase immunohistochemistry quantified with a the Roche RPW image analyzer (Roche Image Analysis Systems, Elon College, NC). DNA ploidy was determined on formalin-fixed, paraffin-embedded Feulgen-stained 5-microns tissue sections of the narrow-bore initial prostate carcinoma biopsies with the Roche RPW image analyzer. The 51% mean positive area E-CD expression in the group of 56 adenocarcinomas was significantly less than the 76% expression level for 15 normal control prostate tissues (P < 0.001). E-CD expression was also decreased in aneuploid (39%) versus diploid tumors (54%, P < 0.001); and in high-grade (44%) versus low-grade lesions (54%; P < 0.01). The 44% E-CD expression level in patients with metastases was lower than the 52% level in the nonmetastatic cases, but this finding was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:E-cadherin expression in prostatic carcinoma biopsies: correlation with tumor grade, DNA content, pathologic stage, and clinical outcome. 753 Aug 50

The prerequisite for a curative resection of metastases is their restriction to the key organs, the liver and lungs, in the sense of a limited dissemination. For long-term prognosis, the type of primary tumor as well as the radical resection of lung and liver metastases is essential. To improve the process of surgical indication and therapy of tumors, clear definitions for the terms "tumor recurrence" and "metastases" have been agreed upon. Research and clinical investigation have led to a better understanding of tumor-regulating factors, some of which are briefly described: Metastasis promoting factors include the lack of E-cadherin, which leads to a local penetration of basal membranes by tumor cells; CD44 seems to play an important role in cell-cell and cell-matrix interactions, apparently increasing the metastatic potential of tumors and reducing the long-term survival of patients. High levels of urokinase in primary tumors are also associated with a poorer prognosis, as well as plasminogen inactivator inhibitor PAI II, which plays a crucial role in tumor growth. Positive findings in bone marrow aspirates of patients with different malignancies, stained for cytokeratin 18, either are associated with higher recurrence rates in colon and breast cancer or can be correlated to the prognosis of patients with gastric cancer. Technical aspects of surgery for hepatic, pulmonary and skeletal metastases are presented and discussed with respect to curative and palliative indications.
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PMID:Surgical treatment of tumor metastases: general considerations and results. 753 64

Enhanced expression of the epidermal growth factor receptor and loss of expression of the cell-cell adhesion molecule E-cadherin have each been implicated in the development and progression of a variety of human malignancies. There is some evidence for a correlation between the expression of these two genes and the possible influence of the E-cadherin gene product on the expression of epidermal growth factor receptor. We evaluated 33 matched primary and metastatic non-small cell lung cancer specimens using immunohistochemical staining. There was a statistically significant correlation between staining intensity for epidermal growth factor receptor and E-cadherin in the primary tumors (P = 0.017, by Spearman correlation test). No difference was noted between primary and metastatic disease for either gene product. Studies that include clinical data are needed to clarify the significance of these findings and to evaluate whether these markers will help predict prognosis in tumors.
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PMID:Immunohistochemical evaluation of E-cadherin and epidermal growth factor receptor in non-small cell lung cancer. 756 48

Considerable evidence now exists to support an important role for the E-cadherin-mediated cell-cell adhesion pathway as a suppressor of the invasive phenotype in adenocarcinoma cells. Previous studies have found that this pathway is frequently aberrant in prostate cancers, particularly those that are likely to metastasize. In this study, we report on the effects of re-establishment of this pathway in a prostate cancer cell line, PC-3, in which this adhesion system is dysfunctional by virtue of a deletion of the gene that codes for alpha-catenin, an E-cadherin-associated protein necessary for normal E-cadherin function. Re-expression of alpha-catenin was accomplished either by transfection of PC-3 cells with a copy of the alpha-catenin cDNA under the control of a heterologous promoter or by microcell-mediated transfer of chromosome 5, which contains the alpha-catenin gene and its normal regulatory elements. In both cases, re-expression of alpha-catenin is associated with a similar, dramatic alteration in cell morphology, whereby extensive cell-cell contact is observed. In the case of transfection of the cDNA, this expression is only transient, because the transfected cells either cease to proliferate or, more commonly, revert to the parental phenotype with concomitant cessation of alpha-catenin expression. In contrast, cells containing one or more copies of microcell-transferred chromosome 5 express alpha-catenin in a stable manner and continue to proliferate. Upon injection into nude mice, these latter cells are no longer tumorigenic, or form only slowly growing tumors with greatly extended doubling times when compared to the parental PC-3 cells. During passage in culture, clones that contain only one transferred copy of chromosome 5 reproducibly revert to the parental phenotype. This reversion is associated with loss of the chromosome 5 region containing the alpha-catenin gene and consequent loss of alpha-catenin expression, as well as re-emergence of tumorigenicity. Transfer of chromosome 5 into prostate cancer cells that are E-cadherin negative does not result in either morphological transformation or suppression of tumorigenicity, suggesting that these effects of alpha-catenin expression are dependent upon concomitant expression of E-cadherin. These data demonstrate the tumor suppressive ability of chromosome 5 in the PC-3 prostate cancer cells and suggest that re-expression of alpha-catenin with resultant restoration of E-cadherin function plays a critical role in this process.
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PMID:Chromosome 5 suppresses tumorigenicity of PC3 prostate cancer cells: correlation with re-expression of alpha-catenin and restoration of E-cadherin function. 758 12


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