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

Adhesion molecules are substances which are involved in the interactions between cells, and between cells and the extracellular matrix in both benign and malignant tissues. Two members of this group--intercellular adhesion molecule-1 (ICAM-1) and MUC18--have previously been found to be expressed on melanoma; however, studies seeking a correlation between expression and metastatic behaviour have yielded conflicting results. In this study we investigated the expression of these two antigens and that of a number of other adhesion molecules [VCAM-1, ELAM, and the neural cell adhesion molecule (NCAM)] on a range of benign and malignant melanocytic lesions. Both ICAM-1 and MUC18 were found on a high percentage of all melanocytic lesions including benign naevi. VCAM-1 was found to be expressed on 79 per cent of benign naevi, 62 per cent of primary melanomas less than 1.5 mm in depth, and 6 per cent of thick primaries. The antigen was present on 14 per cent of lymph node metastases and on no extranodal deposits. This suggests that loss of melanoma cell adhesion mediated by VCAM-1 may be important in the development of metastatic melanoma.
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PMID:A study of adhesion molecules as markers of progression in malignant melanoma. 137 91

Thirteen specimens of metastatic malignant melanoma resected from eight patients undergoing craniotomy were analyzed cytogenetically from short-term cultures. All patients had chromosome 1 aberrations, as did three of four patients with metastases only to extracranial sites. Both groups had variable involvement of chromosomes 3, 6, 7, and 8. Only those with brain metastases had 11q and/or 17q involvement in six of eight patients. In reported cases of nonbrain metastases, when chromosome 11 was involved, the short arm was usually deleted or replaced through translocation; on the contrary, in reports on patients with brain metastases, the long arm of chromosome 11 was deleted at q23 or was the recipient of a translocation at q23, and/or 17q was present as an isochromosome. These aberrations were similar to those found in the patients with brain metastases in this report. Two patients undergoing brain resections did not show 11q or 17q aberrations, one near diploid with t(10;19) and the other near hexaploid with few structural rearrangements. The neural cell adhesion molecule gene is located near 11q23, and the neural growth factor receptor is located near 17q21-q22. The relevance of these genes to brain metastases in melanoma is under investigation.
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PMID:Preferential chromosome 11q and/or 17q aberrations in short-term cultures of metastatic melanoma in resections from human brain. 148 60

To identify molecules which may be functionally associated with the development of metastasis in human melanoma, monoclonal antibodies which discriminate between benign and malignant melanocytic lesions in situ were selected. Biochemical studies and cDNA cloning identified the antigens HLA-DR, ICAM-1 and MUC18 which showed an expression pattern on primary tumors correlating with vertical tumor thickness, the most predictive parameter for the development of metastasis in melanoma. ICAM-1 and MUC18 show sequence similarity to a family of cell adhesion molecules which include the neural cell adhesion molecule NCAM. Both HLA-DR and ICAM-1 can be induced on melanoma cells by lymphokines, suggesting a role of the mononuclear cell infiltrate in the control of tumor cell phenotype. Knowledge of the normal function of these molecules allows one to hypothesize how they may contribute to the successful development of metastases.
Invasion Metastasis 1989
PMID:Functional aspects of three molecules associated with metastasis development in human malignant melanoma. 257 17

The MUC18 antigen is an integral membrane glycoprotein of 113 kDa whose expression on primary human melanomas correlates with poor prognosis and the development of metastatic disease. MUC18 is expressed only sporadically in benign melanocytic nevi and thin primary melanomas that have a low probability of metastasizing. However, with increasing tumor thickness, MUC18 expression becomes more frequent and it is found on 80% of advanced primary tumors and metastases. MUC18-encoding cDNA clones were obtained by screening a human melanoma phage lambda expression library with monoclonal antibodies produced against the denatured antigen. The deduced sequence of 603 amino acids consists of a signal peptide, five immunoglobulin-like domains, a transmembrane region, and a short cytoplasmic tail. The highest sequence similarity is with a group of nervous system cell adhesion molecules, which includes neural cell adhesion molecule (N-CAM). The close structural relationship with these molecules suggests that MUC18 may also be a developmentally regulated cell adhesion molecule.
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PMID:MUC18, a marker of tumor progression in human melanoma, shows sequence similarity to the neural cell adhesion molecules of the immunoglobulin superfamily. 260 81

Alterations in the adhesive mechanisms of cancer cells are likely to play an important role in determining the invasive or metastatic potential of these cells. An understanding of these alterations at the molecular level is now within reach, due to recent progress in the identification and characterization of several cell adhesion molecules (CAMs). Two of these molecules, the neural cell adhesion molecule N-CAM and the liver cell adhesion molecule L-CAM, are expressed on a variety of cell types from early embryos and throughout adult life, and appear to play several important roles in early inductive events, formation of specific intercellular connections, and maintenance of adult tissues. Two other molecules, the neuron-glia adhesion molecule Ng-CAM and a molecule involved in the specific adhesion of lymphocytes, appear to be more restricted in their developmental expression and function. The molecular characterization of N-CAM made possible for the first time an examination of the effects of transformation on the expression of a defined cell adhesion molecule. In both established cell lines from rat cerebellum and embryonic chick neuroepithelial cells, transformation by Rous sarcoma virus caused a large reduction in expression of N-CAM. In both cases, the N-CAM-mediated adhesion was correspondingly reduced. The neuroepithelial cells also became more highly motile after transformation. The decrease in N-CAM coupled with this increase in cell motility may significantly enhance the invasiveness of these cells. Other surface antigens have also been identified that may be involved in essential steps of invasion and metastasis. Such studies represent the initial step toward a detailed understanding of the role of CAMs in the various steps of metastasis. The accessibility of CAMs on tumor cell surfaces, and the availability of specific antibodies to these components suggests that reagents may become available in the near future that will offer new opportunities for preventing the formation of metastases.
Cancer Metastasis Rev 1985
PMID:Molecular mechanisms of cell adhesion in normal and transformed cells. 388 82

Tumor cell adhesion, detachment, and aggregation play an important part in tumor invasion and metastasis, and a variety of cell adhesion molecules have been found on tumor cells. Cell adhesion molecules, including those of the immunoglobulin superfamily, are associated with the development of metastatic behavior in cutaneous melanomas. The neural cell adhesion molecule (NCAM) belongs to this family. To investigate its possible role in the development metastatic behavior of uveal melanomas, the authors studied immunohistochemically the expression of NCAM by using an antibody that recognizes all three major isoforms of NCAM and an antibody that recognizes the HNK-1 epitope present on some isoforms of NCAM. The authors studied 32 primary uveal melanomas from 32 patients (among these, 12 were rapidly metastasizing and 16 slowly metastasizing) and 29 metastases from 19 patients. From 13 patients the primary, as well as the metastatic, tumors were available. With one exception, all HNK-1 positive primary and metastatic tumors were also positive for NCAM. NCAM was significantly more expressed in aggressive, rapidly metastasizing primary tumors (P = .02 and .04, respectively) and in metastases. HNK-1 was significantly (P = .04) more expressed in larger tumors. In liver metastases HNK-1 immunoreactivity was significantly (P = .005) less frequently expressed than NCAM. Therefore, NCAM isoforms that lack the HNK-1 epitope might play a role in the organ specific metastatic behavior of uveal melanomas.
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PMID:Neural cell adhesion molecule distribution in primary and metastatic uveal melanoma. 759 Jun 90

A glioma cell line, CNS-1, was developed in the inbred Lewis rat to obtain a histocompatible astrocytoma cell line with infiltrative and growth patterns that more closely simulate those observed in human gliomas. Rats were given weekly intravenous injections for a six month period with N-nitroso-N-methylurea to produce neoplasm in the central nervous system. Intracranial tumor was isolated, enzymatically and mechanically digested, and placed into culture. The tumor cell line injected subcutaneously on the flanks of Lewis rats grew extensively in situ as cohesive tumor masses but did not metastasize. Intracranially, CNS-1 demonstrated single cell infiltration of paranchyma and leptomeningeal, perivascular, and periventricular spread with expansion of the tumor within choroid plexus stroma. CNS-1 cells titrated in right frontal brain of Lewis rats at 10(5), 5 x 10(5), 10(5), 5 x 10(4) cells per group had mean survival times ranging from 20.5 to 30.2 days. CNS-1 was immunoreactive for glial fibrillary acidic protein, S100 protein, vimentin, neural cell adhesion molecule, retinoic acid receptor alpha, intercellular adhesion molecule, and neuron specific enolase. The CNS-1 cells commonly had one or more trisomies of chromosomes 11, 13 or 18; losses, possibly random, of chromosomes (3, 5, 19, 30, X or Y) were noticed, and a marker chromosome made up of approximately 3 chromosomes was usual. Comparisons of CNS-1 to 9L gliosarcoma tumor were made. The glial CNS-1 tumor model provides an excellent system in which to investigate a variety of immunological therapeutic modalities. It spreads within brain in a less cohesive mass than 9L and is accepted without rejection in non-central nervous system sites by Lewis rats.
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PMID:A rat glioma model, CNS-1, with invasive characteristics similar to those of human gliomas: a comparison to 9L gliosarcoma. 776 95

The neural cell adhesion molecule (NCAM) was recently suggested as a marker for small-cell lung cancer (SCLC). Immunohistochemical analysis demonstrated the presence of the NCAM in 78% of SCLC patients and in 25% of patients with other cancer forms. NCAM was proposed to be the most sensitive marker for SCLC, and it may also be an important prognostic marker for SCLC. We used a competitive ELISA to analyze the concentrations of NCAM in sera from 96 SCLC patients, 16 patients with non-SCLC, 4 patients with other cancer forms, and 16 healthy controls. All sera were collected at the time of diagnosis, before the patients received chemotherapy. The polyclonal antibody used in the assay recognized all three isoforms of NCAM. The concentration of NCAM was related to clinical parameters of the patients such as age, sex, blood group status, stage of disease, organ site involvement of metastases, survival, and expression of the ganglioside fucosyl-GM1 (FucGM1). Sera were considered positive if NCAM concentrations were higher than the mean concentration of healthy controls plus two standard deviations. Twenty-two percent of the sera from SCLC patients were positive for NCAM. No difference in concentration was found between SCLC patients with localized and extensive disease. Serum from one patient with cancer of the thyroid, but no sera from non-SCLC patients or normal healthy controls, was positive. The expression of NCAM did not correlate to any of the clinical parameters, and no correlation was found to the other serum marker, FucGM1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New serum markers for small-cell lung cancer. II. The neural cell adhesion molecule, NCAM. 798 39

The WC5 rat cerebellar cell line, infected with a Rous sarcoma virus (RSV) that is temperature-sensitive for pp60v-src transformation, expresses high levels of the neural cell adhesion molecule, N-CAM, when grown at the non-permissive temperature for pp60v-src activity. At the permissive temperature, N-CAM expression is 4- to 10-fold reduced and the cells aggregate poorly. To evaluate the effects of variations in N-CAM expression, we compared the invasive ability of transformed WC5 cells that express low levels of N-CAM with transformed cells in which N-CAM-mediated adhesion was restored. WC5 cells were transfected with expression vectors containing cDNAs encoding the 120 or 180 kDa forms of chicken N-CAM linked to constitutive promoters. Several permanently transfected lines that expressed chicken N-CAM at the cell surface were isolated. These cell lines showed enhanced aggregation at the permissive temperature relative to untransfected WC5 cells or cells transfected with control constructs. By comparing the ability of control and transfected WC5 cells to invade reconstituted extracellular matrix, we tested the effect of variations in N-CAM-mediated adhesion on invasion. Clones that expressed high levels of N-CAM showed invasion rates that were similar to control cells, indicating that increasing N-CAM-mediated adhesion does not inhibit the invasiveness of RSV-transformed WC5 cells.
Clin Exp Metastasis 1993 Jul
PMID:Increasing N-CAM-mediated cell-cell adhesion does not reduce invasion of RSV-transformed WC5 rat cerebellar cells. 839 6

One crucial step in tumor metastasis is detachment of cells from the primary lesion. This involves down-regulation of homophilic binding intercellular adhesion molecules. To determine whether this occurs in metastasis of human small-cell lung cancer to lymph nodes, we examined expression of E-cadherin, carcinoembryonic antigen (CEA), and neural cell adhesion molecule (NACM) on cells from patients with small-cell lung cancer, some cells were obtained from primary lesions and others from lymph-node metastases. Cells in all of the five lines from primary lesions expressed E-cadherin, unlike those in all of the five lines from lymph-node metastases. Cells in all of the five lines from primary lesions expressed CEA, as did those in only one of the five cell lines from lymph-node metastases. Cells in lines from primary and metastatic lesions did not differ in the expression of NCAM (4/5 positive). Expression of E-cadherin and of CEA were closely correlated. Because E-cadherin and CEA are involved in the binding of epithelial cells, these findings demonstrate that metastasis of small-cell lung cancer to lymph nodes is associated with a lack of the epithelial intercellular adhesion molecules E-cadherin and CEA. The expression of these molecules is involved in the metastasis of small-cell lung cancer to lymph nodes.
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PMID:[Difference in expression of epithelial adhesion molecules between primary and metastatic lesions in small-cell lung cancer]. 895


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