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)

The reactivity of four monoclonal antibodies (MAbs) directed against IFN-gamma inducible antigens with melanocytic cells was investigated in the course of local and systemic tumor progression of human malignant melanoma. Frozen sections of histologically defined melanocytic tissues at different stages of progression were stained with these MAbs using an indirect immunoperoxidase technique. The reactivity of MAbs Me15/B3 and Me15/F9, directed against two different epitopes of a 90-kDa molecule, was found to correlate with melanoma progression. Indeed, a significantly lower percentage of small than of advanced primary melanomas or metastases stained positively. A differential staining of nevocytic and dysplastic nevi was further observed for these two MAbs, which were also non-reactive with normal skin melanocytes. The reactivity of MAb Me14/D12, which identifies the intercellular adhesion molecule ICAM-1 and MAb Mel14/F12, directed against a 40-kDa molecule, was found to be independent of the Breslow thickness of primary melanomas. Both the latter MAbs stained a high proportion of nevocytic and dysplastic nevi. The co-expression of the surface molecules defined by MAbs Me14/D12, Me15/B3 and Me15/F9 in the course of melanoma progression was also analyzed. The frequency of this co-expression increased according to the Breslow thickness of primary melanomas. In addition, up to 100% of metastases, as opposed to 20% of dysplastic nevi, were found to be simultaneously stained by these three MAbs. It is therefore conceivable that high-risk melanocytic lesions might be identified by the use of a combination of MAbs directed against IFN-gamma regulated antigens.
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PMID:The differential reactivity of cells of the melanocytic lineage with four monoclonal antibodies against IFN-gamma inducible molecules. 134 19

We recently produced the monoclonal antibody E48 as a specific reagent for squamous cell carcinomas. In our ongoing investigations to use E48 for clinical tumor detection and therapy, fundamental aspects of the antigen have to be elucidated and practical applications of the antibody have to be tested in a preclinical model. Immunoelectron-microscopic studies localized the E48 antigen along the cell surface and in between desmosomes, suggesting that the antigen serves as an adhesion molecule. To evaluate the usefulness of E48 for radioimmunodetection of neck node metastases, nodes from 20 neck dissection specimens were tested. A strong reactivity was observed. Furthermore, F(ab')2 fragments of E48 were compared with the complete IgG E48 for selective tumor detection in an animal model. It was demonstrated that E48 F(ab')2 fragments localize faster and reach higher tumor-nontumor ratios than the whole molecule.
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PMID:Detection of squamous cell carcinoma xenografts in nude mice by radiolabeled monoclonal antibody E48. 174 35

Current evidence indicates that the localization and extravasation of neutrophils is a complex process involving several adhesion molecules with apparently distinct functions, and a highly coordinated and dynamic interplay between the neutrophil and the endothelial cell that is influenced by the shear forces present at the interface between these two cell types. Chemotactic stimulation of the neutrophil not only induces directed locomotion but markedly alters the surface expression and functions of the neutrophil adhesion molecules, having both an upregulating and downregulating influence. Cytokines such as interleukin 1 induce the synthesis and surface expression of endothelial adhesion molecules such as ICAM-1 and ELAM-1, and stimuli such as thrombin and histamine induce the rapid mobilization to the endothelial surface of another adhesion molecule, GMP-140. Transendothelial migration of neutrophils in most settings both in vitro and in vivo appears to require CD18 integrins on the neutrophil and ICAM-1 on the endothelial cells. This is most clearly demonstrated by the genetic deficiency of CD18 in humans, dogs and cattle, where neutrophil extravasation at most inflammatory sites is almost completely absent. Though the coordinated functions of the various neutrophil and endothelial adhesion molecules are highly efficient in promoting neutrophil extravasation, there has been relatively little investigation of their utilization in tumor cell dissemination. Recent results indicate that such studies may prove fruitful. For example, some adenocarcinoma cell lines express the complex carbohydrate (sialyl Lewis x) recently shown to be a ligand for ELAM-1.
Cancer Metastasis Rev 1991 May
PMID:PMN adhesion and extravasation as a paradigm for tumor cell dissemination. 191 73

Tumor H-59 is a variant of the Lewis lung carcinoma which is metastatic to the liver. In previous studies we have shown that liver metastasis in this tumor model correlates with adhesion in vitro to hepatocyte monolayers (Brodt, P., Clin. Exp. Metastasis, 7: 525-539, 1989). In an attempt to identify the adhesion molecule(s) involved, monoclonal antibodies were produced. One monoclonal antibody (MAb C-11) was highly specific to hepatocyte-adherent tumor cells. The antibody (an IgG1) and F(ab)2 fragments blocked tumor cell attachment to hepatocytes while having no effect on tumor cell adhesion to basement membrane proteins coated onto culture dishes. Western blot analysis of solubilized 11-59 plasma membranes or cell lysates showed that the antibody recognizes an Mr 64,000 protein. Treatment with N-glycosidase F prior to Western blot analysis revealed that N-linked carbohydrate residues constitute approximately 43% of the total weight of this molecule. This glycoprotein is only weakly expressed on tumor M-27, a lung-specific subline of the Lewis lung carcinoma (Brodt, P., Cancer Res., 46: 2442-2448, 1986), is undetectable in plasma membrane preparations obtained from spleen cells and thymocytes, but can be detected on cultured hepatocytes and in hepatocyte cell lysates. Pretreatment of the hepatocytes with MAb C-11 also resulted in inhibition of tumor cell adhesion. These results suggest that this glycoprotein mediates the attachment of H-59 cells to hepatocytes.
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PMID:Identification of an Mr 64,000 plasma membrane glycoprotein mediating adhesion of tumor H-59 cells to hepatocytes. 205 93

Recent studies indicate that chemotherapy is a cause for thrombosis in breast cancer patients. We performed experiments to determine whether the enhanced thrombosis was due, in part, to an effect of chemotherapy on endothelial cell reactivity. Heparinized blood samples were obtained from stage II breast cancer patients receiving monthly adjuvant chemotherapy consisting of cyclophosphamide, epirubicin and 5-fluorouracil. Cultured human endothelial cells were incubated with the plasmas for 2 h, and then the reactivity of the endothelial cells to normal donor platelets was determined isotopically. Endothelial cell reactivity was increased when the endothelial cells were incubated with the post-chemotherapy plasmas. The plasma effect persisted after the chemotherapy drugs were cleared from the circulation, but this plasma effect was abolished when the plasmas were heat-inactivated. Furthermore, the increase in endothelial cell reactivity correlated with the level of interleukin-1 present in the post-chemotherapy plasmas. Finally, the increased endothelial cell reactivity was inhibited by the GRGDS peptide, or by an antibody to the endothelial cell vitronectin receptor. These observations suggest that chemotherapeutic drugs alter endothelial cell reactivity to platelets by inducing the release of interleukin-1 which, in turn, facilitates adhesion molecule expression on the endothelial cell surface. If so, these observations provide a possible explanation for one mechanism which may contribute to the thrombogenic effect seen in breast cancer patients undergoing chemotherapy.
Clin Exp Metastasis
PMID:Chemotherapy enhances endothelial cell reactivity to platelets. 214 53

From the highly metastatic TAM2D2 T-cell hybridoma we have previously generated three independent mutants that were deficient in the surface expression of the adhesion molecule Leukocyte Function-associated Antigen 1 (LFA-1). Both the invasive capacity and the metastatic potential of these mutants were greatly reduced compared with TAM2D2 cells (F.F. Roossien et al., J. Cell Biol., 108: 1979-1985, 1989). We now show that, during in vivo transplantation, LFA-1 is reinduced in these mutants. From such revertant cell populations obtained after two to three i.p. passages, we isolated clones with different LFA-1 levels. Of each of the three mutant cell lines, the clone with the highest and the one with the lowest LFA-1 level were selected for further study. Invasiveness in fibroblast monolayers correlated strongly with LFA-1 level; i.e., the low-LFA-1 clones (mean LFA level, approximately 10% of TAM2D2) invaded as poorly as the original mutants, whereas the high-LFA-1 clones (greater than 25% of TAM2D2) were highly invasive. Metastatic potential was determined after tail vein injection of 10(6) cells in syngeneic AKR mice. A difference was observed between high- and low-LFA-1 clones, albeit less striking than previously found between LFA-1-negative mutants and parental TAM2D2 cells. The high-LFA-1 clones developed metastases in more mice (76 versus 43%) and earlier (mean survival, 30 versus 37 days). These results provide further evidence for an important role of LFA-1 in invasion and metastasis of mouse T-cell hybridomas.
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PMID:Invasive and metastatic capacity of revertants of LFA-1-deficient mutant T-cell hybridomas. 218 97

Tumor necrosis factor (TNF-alpha) was compared to immune interferon (IFN-gamma) for its ability to modulate the expression and shedding of HLA antigens, of intercellular adhesion molecule I (ICAM I) and of high-molecular-weight melanoma-associated antigen (HMW MAA) by a panel of melanoma cell lines. The latter included the melanoma cell line MeWo and its metastatic variant MeM 50-10, which display differential susceptibility to modulation of HLA class-II antigens by IFN-gamma and the cell lines SK-MEL-93-DX-2 and SK-MEL-93-DX-3, which originated from anatomically distinct metastases in patient DX. TNF-alpha enhanced the expression of HLA class-I antigens on all 7 melanoma cell lines tested, although to a lower extent than IFN-gamma and the combination of IFN-gamma and TNF-alpha. TNF-alpha displayed a differential effect on the expression of HLA class-II antigens by the 7 melanoma cell lines: it enhanced it on 3 out of the 4 cell lines with constitutive expression of HLA class-II antigens and induced them on 1 of 3 cell lines without detectable expression of these antigens. The effects of IFN-gamma were different since it enhanced HLA class-II antigens on the 4 cell lines with constitutive expression of these antigens and induced them on 2 out of the remaining 3 lines. Interestingly, both TNF-alpha and IFN-gamma enhanced the expression of HLA class-II antigens by SK-MEL-93-DX-3 cells. On the other hand only TNF-alpha induced the expression of HLA class-II antigens by MeWo cells and only IFN-gamma induced such expression by MeM 50-10 cells and by SK-MEL-93-DX-2 cells. The effect of the combination of TNF-alpha and IFN-gamma was similar to that of the individual cytokines. Both TNF-alpha and IFN-gamma displayed a differential effect on the expression of the gene products of the HLA-D region by the melanoma cell lines. Northern blot analysis with HLA-DR beta-, DQ beta- and DP beta-specific probes suggests that the modulation of HLA class-II antigens by both cytokines reflects transcriptional and post-transcriptional events. TNF-alpha enhanced the expression of ICAM-I on all the melanoma cell lines, although to a lower extent than IFN-gamma and the combination of IFN-gamma and TNF-alpha. Lastly, neither TNF-alpha nor IFN-gamma displayed a marked effect on the expression of HMW-MAA by the melanoma cell lines tested.
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PMID:Differential modulation by tumor necrosis factor and immune interferon of HLA class-II antigens expressed by melanoma cells. 250 38

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

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

CD44 is the transmembrane adhesion molecule which binds hyaluronate. The gene encoding CD44 is found on chromosome 11p and comprises 20 exons. Differential splicing of the 10 extracellular juxtamembranous exons (v1-10) generates the major isoforms of CD44. The major CD44 isoform found on hematopoetic cells (CD44s) contains none of the variably expressed exons, while the major isoform expressed on epithelial cells [CD44(v8-10)] contains exons v8-10. Metastasis-specific isoforms of CD44 were first documented in a model of rat pancreatic adenocarcinoma [CD44(v4-7), CD44(v6-7)] and subsequently in other cancers. This study is the first characterization of CD44 isoforms in primary and metastatic human pancreatic adenocarcinomas. CD44 isoforms were analyzed in specimens of 15 primary and 6 metastatic pancreatic adenocarcinomas as well as in 6 specimens of control pancreata by two different methods. Radiolabeled reverse transcriptase-PCR coupled with 8% PAGE allowed analysis of the major isoforms of CD44, while Southern blot hybridization with [alpha-32P]dCTP-labeled probes permitted analysis for metastasis-specific CD44 isoforms containing CD44(v6) or CD44(v8-10). No differences in the expression of CD44(v8-10) and CD44s were found among the primary and metastatic pancreatic adenocarcinomas, and control specimens of pancreata. However, a novel CD44(v6) isoform was found in metastatic lesions and may represent the human homologue of the rat pancreatic adenocarcinoma metastasis-associated CD44 isoform.
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PMID:CD44 isoform expression in primary and metastatic pancreatic adenocarcinoma. 753 74


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