Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

E- and N-cadherins are proteins involved in intercellular adhesion and are localized, e.g., in the adherens junctions of epithelial cells. Kidney tubules express these molecules in a distinctive pattern, the expression of N-cadherin being restricted to proximal tubules and that of E-cadherin to distal tubules and collecting ducts. Renal cell carcinomas (RCCs) and oncocytomas are considered to originate from these tubular epithelia. To find out whether cadherins could serve as markers for a cellular origin of these tumors, we studied the expression of E- and N-cadherins in RCCs and oncocytomas, in cell lines derived from RCCs as well as in tumors grown in nude mice. Most RCCs co-expressed E- and N-cadherins, as did 2 of the 4 cell lines studied. The expression pattern did not correlate with the histological grade of the tumors, and even the least differentiated tumors, as well as metastases, showed expression of cadherins. Renal oncocytomas expressed E-cadherin but not N-cadherin, which is in line with previous studies that have proposed a collecting duct origin for these tumors. Papillary renal neoplasms, a separate entity usually not classified as RCC, expressed neither of the cadherins studied despite the abundant expression of beta-catenin. Our results suggest that most RCCs co-express the characteristic adhesion molecules of both proximal and distal tubules, which makes it questionable whether the origin of these tumors can be reliably located to any distinct part of the renal tubule. Our results also suggest that in RCCs the increased histological grade is not directly associated with changes in the expression of either of the cadherins, indicating other mechanisms underlying the deficient capacity to form polarized tubular structures.
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PMID:Expression of E- and N-cadherin in renal cell carcinomas, in renal cell carcinoma cell lines in vitro and in their xenografts. 855 Feb 43

The HaCa4 cell line, derived from a mouse skin carcinoma induced by Harvey murine sarcoma virus, is highly tumorigenic when injected into nude mice and produces multiple metastases in the lungs. HaCa4 cells express high levels of viral Ha-ras oncogene products, anomalously synthesize the embryonic/simple epithelial keratin K8, and have lost the expression of the cell-cell adhesion receptor E-cadherin (E-CD). E-CD(+) cell clones (E62 and E24), obtained by transfection of an exogenous E-CD cDNA into HaCa4 cells, had a decreased ability to migrate through type IV collagen matrices. However, the E-CD (+) E62 clone remained as metastatic as the parental cell line, whereas the E24 clone, which does not take up the exogenous cDNA but spontaneously switches on the endogenous E-CD gene, suppressed the metastatic phenotype although it maintained its tumorigenicity. E24 cells had fivefold to sixfold lower levels of viral Ha-ras mRNA and p21 protein than the other cell lines. In addition, they did not synthesize K8 but rather switched on keratin K19. The comparison of E-CD proteins synthesized by E62 and E24 cell lines revealed no structural or functional differences because both localized at cell-cell contacts and associated with alpha-catenin, beta-catenin, and plakoglobin. Furthermore, E-CD was still expressed in metastatic lung nodules produced by E62 cells. These results suggest that suppression of the metastatic phenotype in E24 cells occurs independently of E-CD expression and correlates with decreased levels of the oncogenic ras p21 protein.
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PMID:Suppression of the metastatic phenotype of a mouse skin carcinoma cell line independent of E-cadherin expression and correlated with reduced Ha-ras oncogene products. 859 77

Immunohistochemical studies have suggested that E-cadherin may be a useful prognostic marker in prostate cancer. Previous studies have depended on cryostat sections of tissues selected grossly. Many prostate cancers, even when extensive, are not visible grossly; many others cannot be demarcated sharply grossly. The wide applicability of prognostic markers after total prostatectomy will depend upon methods that can be applied to tissue selected based upon the histopathological examination of the entire prostate. Our purpose was to investigate the possibility that E-cadherin could be demonstrated in paraffin-embedded whole prostates and metastatic prostate cancer. Microwaving in citrate buffer was the best of five methods tested for the demonstration of E-cadherin in paraffin-embedded prostate and was used to investigate 53 primary prostate cancers from 44 patients and lymph node metastases from 14 patients. Metastases of prostate cancer to lymph nodes expressed less (P = 0.008) E-cadherin than primary prostate cancers. The expression of E-cadherin correlated with the histopathological differentiation (Gleason grade) of primary prostate cancers (P = 0.03, Ptrend = 0.003). The use of monoclonal anti-human E-cadherin (HECD-1) with microwaving in citrate buffer followed by immunoperoxidase staining with heavy metal enhancement for the demonstration of E-cadherin in paraffin-embedded tissue will, for the first time, allow the use of archival tissue for prognostic studies of E-cadherin in prostate cancer and other tissue. Our results are consistent with the hypothesis that aggressive prostate cancers exhibit decreased expression of E-cadherin and demonstrate the feasibility of long-term prognostic studies of this molecule in the usually multiple prostate cancers found in whole, formalin-fixed, paraffin-embedded resected prostates.
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PMID:Expression of E-cadherin in primary and metastatic prostate cancer. 862 9

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

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

Transition from an epithelioid (e-) to a fibroblastic (f-) morphotype marks invasiveness in clinical and experimental cancer. To understand better the factors influencing such transitions, we have subcloned and manipulated mouse mammary gland (NMuMG) cell cultures and compared the invasive phenotype of multiple subclones in vitro and in vivo. Cell lines with an e-morphotype expressed E-cadherin homogeneously and were not invasive in vitro. Cells with an f-morphotype were E-cadherin-negative and became fully invasive in vitro upon expression of the ras oncogene. Invasive tumors were produced in node mice after subcutaneous injection of e-type or f-type cells. These tumors showed cystic, glandular and undifferentiated structures. Tumors from f-type cells were E-cadherin-negative whereas e-type tumors stained heterogeneously in immunohistochemical preparations. Our observations demonstrate the impact of the micro-ecosystem on the invasive phenotype, with in vivo downregulation of E-cadherin and stimulation of the e- to f-morphotype transition.
Clin Exp Metastasis 1996 May
PMID:Morphotypic plasticity in vitro and in nude mice of epithelial mouse mammary cells (NMuMG) displaying an epithelioid (e) or a fibroblastic (f) morphotype in culture. 867 83

The molecular mechanisms by which human cancer cells spread to bone are largely unexplored. The process likely involves cell adhesion molecules (CAMs) that are responsible for homophilic and heterophilic cell-cell interactions. One relevant CAM may be the calcium-dependent transmembrane glycoprotein E-cadherin. To investigate the involvement of E-cadherin in breast cancer metastasis to bone, we used an in vivo model in which osteolytic bone metastases preferentially occur after injections of cancer cells directly into the arterial circulation through the left ventricle of the hearts of nude mice. We have found that E-cadherin-negative human breast cancer cells MDA-MB-231 (MDA-231) develop radiographically detectable multiple osteolytic bone metastases and cachexia in this model. However, MDA-231 breast cancer cells that were transfected with E-cadherin cDNA showed a dramatically impaired capacity to form osteolytic metastases and induce cachexia. Histological and histomorphometrical analyses of bones of mice bearing mock-transfected MDA-231 revealed aggressive metastatic tumor, whereas metastatic tumor burden was significantly decreased in the bones of mice bearing E-cadherin-expressing MDA-231. Nude mice bearing E-cadherin-transfected MDA-231 breast cancer cells survived longer than mice bearing mock-transfected MDA-231 breast cancer cells. Anchorage-dependent and -independent growth in culture and tumor enlargement in the mammary fat pad of nude mice were unchanged between mock-transfected and E-cadherin-expressing MDA-231, suggesting that these differences in metastatic behavior are not due to an impairment of cell growth and tumor-igenicity. Our results show the suppressive effects of E-cadherin expression on bone metastasis by circulating breast cancer cells and suggest that the modulation of expression of this CAM may reduce the destructive effects of breast cancer cells on bone.
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PMID:E-cadherin expression in human breast cancer cells suppresses the development of osteolytic bone metastases in an experimental metastasis model. 875 80

The purpose of our study was to determine whether the degree of E- and P-cadherin expression in melanomas correlates with the invasive behavior of the clinical lesions from which the cell lines were derived. Cadherins comprise a family of calcium-dependent cellular adhesion molecules expressed on most cell types that form solid tissues. In the human epidermis, melanocyte cadherin expression may function to maintain the integrity of the epidermal-melanin unit. Employing both immunofluorescence microscopy and fluorescence-activated cell sorter analysis, we localized and quantitated E- and P-cadherin expression on melanoma cell lines derived from primary or metastatic lesions using the monoclonal antibodies HECD-1 and NNC-CAD-299, respectively. Human epidermal melanocytes isolated from neonatal foreskin were evaluated by similar techniques and served as a biologic control. Melanoma cell lines were isolated from primary or metastatic lesions of patients described as having "early," "intermediate," or "advanced disease." Melanoma E- and P-cadherin immunofluorescence, as quantified by fluorescence-activated cell sorter, varied inversely with disease progression. Selected log mean ratios of E-cadherin fluorescence, as compared to human epidermal melanocytes (arbitrarily = 1), ranged from 1.04 in the WM 35 melanoma cell line (low invasive potential) to 0.1 and 0.02 in the WM 983A and 1361A melanoma cell lines (derived from primary lesions with metastases), respectively. Although values for P-cadherin fluorescence were less, the trend of decreasing cadherin amounts with more advanced disease was observed. Melanoma cells appear to express E- and P-cadherin levels inversely related to disease progression. Ultraviolet radiation significantly decreased E- and P-cadherin expression in the human epidermal melanocytes and P-cadherin expression in the WM 35 melanoma cell line (p < 0.05). Although not statistically significant, E-cadherin expression in the WM 35 melanoma cell line decreased substantially. Thus, ultraviolet radiation may have a direct effect on human epidermal melanocytes and melanoma cell attachment through cadherins within the epidermis or tumor nodules.
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PMID:Expression of E and P-cadherin by melanoma cells decreases in progressive melanomas and following ultraviolet radiation. 875 77

Human neonatal foreskin was maintained in organ culture under serum-free, growth-factor-free conditions or in the presence of a combination of growth factors that are known to stimulate keratinocyte proliferation in monolayer culture. Previously, we have shown that normal histology is maintained when growth-factor-free conditions are used but that the epithelium undergoes a hyperproliferative response and invades the dermis in the presence of the exogenous growth factors. In the present study, the tissue was examined by immunofluorescence for expression of alpha 6 and beta 4 integrin components and for E-cadherin. Under growth factor-free conditions, both alpha 6 and beta 4 were localized to the basal surface of epithelial cells in contact with the basement membrane. In contrast, both epitopes were diffusely distributed throughout the basal epithelium in the presence of growth factors. E-cadherin expression was rapidly lost from the tissue in organ culture. This occurred in both the presence and absence of exogenous growth factors. On the basis of these immunochemical results, we conclude that the same changes in alpha 6 and beta 4 expression that are seen in rapidly proliferating keratinocytes and squamous epithelial cell tumors can be seen in the epidermis of organ-cultured skin when it is maintained in the presence of epithelial growth factors. The observed loss of E-cadherin, in contrast, appears to be a consequence of incubation in organ culture.
Invasion Metastasis 1995
PMID:Expression of cell surface adhesion molecules on the epithelium of Organ-cultured skin. 876 93

Changes in the expression and function of adhesion molecules on the surface of cancer cells are important characteristics in the development of gastrointestinal malignancies and might be used in the future as prognostic factors or as new targets for diagnostic and therapeutic approaches. In esophageal cancer a down-regulation of the E-cadherin receptor and the cytoplasmic protein alpha-catenin is associated with tumor dedifferentiation, infiltrative growth and lymph-node metastasis. In gastric cancer a reduction of E-cadherin expression due to gene mutations is restricted to diffuse-type tumors while the occurrence of the CD44-standard and the CD44-9v isoform is significantly related to a higher tumor-induced mortality and a shorter survival time. The CD44-6v isoform is predominantly expressed by intestinal-type gastric carcinomas, giving these tumor cells the ability to perform lymph-node metastasis. In pancreatic cancer the expression of integrin adhesion receptors is significantly altered during the malignant transformation while a loss of the E-cadherin receptor can generate dedifferentiation and invasiveness of pancreas carcinoma cells. There is increasing evidence that integrin receptors as well as different isoforms of the CD44 receptor are altered following the malignant transformation of colonic mucosa into adenomas and invasive carcinomas. The expression of the CD44-6v isoform seems to be associated with an adverse prognosis in colorectal cancer due to the development of tumor metastases. A strong correlation has been observed between the expression of the 67-kDa laminin receptor and the degree of differentiation, the invasive phenotype and the metastatic abilities af colorectal cancer cells. Analyzing the expression of the E-cadherin receptor showed that this receptor may serve as an independent prognostic marker in Dukes' stage B colorectal cancer to identify patients with poor prognosis and designate them for intensive adjuvant therapy and clinical observation after curative surgical tumor treatment.
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PMID:Adhesion receptors in malignant transformation and dissemination of gastrointestinal tumors. 877 62


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