Invasion & metastasis最新文献

{"title":"Expression of adhesion factors and degrading proteins in primary and secondary glioblastomas and their precursor tumors.","authors":"D S Tews,&nbsp;A Nissen","doi":"10.1159/000024520","DOIUrl":"https://doi.org/10.1159/000024520","url":null,"abstract":"<p><p>In tumor tissue specimens of 27 primary and 17 secondary glioblastomas and the precursor lesions, the immunohistochemical expression patterns of the membrane protein CD44s, the basal lamina proteins laminin, collagen IV, and fibronectin, the lectin galectin-3 recognizing tenascin and N-CAM as well as of the matrix-degrading enzymes matrix metalloproteinase MMP-2 and MMP-9, and cathepsin D were studied. Besides expression of basal lamina proteins in vessels, all glioblastomas and the precursor lesions showed strong immunoreactivity of CD44s, tenascin, galectin-3, and N-CAM which were restricted to solid tumor masses. Present in solid tumor areas, MMP-2, MMP-9 and cathepsin D were also strongly expressed by single tumors cells invading adjacent brain tissue at the infiltrative margin. Neither the expression pattern in primary and secondary glioblastomas nor in the precursor tumors revealed significant differences. There was also no intraindividual constant expression pattern during glioma progression or correlation with malignancy. Restricted expression of CD44s, galectin-3, tenascin and N-CAM in solid tumor masses seems to contribute to homotypic tumor cell adhesion while single tumor cells abolish this expression profile and acquire invasive activities by expression of cathepsin D, MMP-2 and MMP-9.</p>","PeriodicalId":14452,"journal":{"name":"Invasion & metastasis","volume":"18 5-6","pages":"271-84"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000024520","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21580844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transepithelial migration of neutrophils.","authors":"D Huber,&nbsp;M S Balda,&nbsp;K Matter","doi":"10.1159/000024500","DOIUrl":"https://doi.org/10.1159/000024500","url":null,"abstract":"<p><p>Neutrophils are a key cell type of nonadaptive immune system and are the first phagocytic cell type that reaches mucosal inflammatory sites. On the last stage of their journey from the blood stream to a mucosal surface, neutrophils cross a generally sealed epithelium by migrating along the paracellular pathway to the luminal side of the epithelial layer. This last step involves a specific receptor-mediated adhesion event of the neutrophil to the epithelium, followed by a rapid and highly coordinated reversible opening of the epithelial intercellular junctions that allows the transmigration of the neutrophils. Although we do not yet understand the molecular mechanisms that mediate this transmigration process, the last years witnessed the discovery of the first neutrophil and epithelial cell surface proteins critically involved in transepithelial migration of neutrophils.</p>","PeriodicalId":14452,"journal":{"name":"Invasion & metastasis","volume":"18 2","pages":"70-80"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000024500","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21233471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distribution of non-diploid flow-cytometric DNA indices and their relation to the nodal metastasis in squamous cell carcinomas of the head and neck.","authors":"J Wennerberg,&nbsp;B Baldetorp,&nbsp;P Wahlberg","doi":"10.1159/000024511","DOIUrl":"https://doi.org/10.1159/000024511","url":null,"abstract":"<p><p>Squamous cell carcinomas of the head and neck (HNSCC) evolve from diploid epithelial cells of the mucosa. At the time of diagnosis about two thirds of clinically diagnosed HNSCC are non-diploid according to flow-cytometric (FCM) analysis, indicating that during tumour progression there must be an acquisition and accumulation of chromosomal aberrations. At diagnosis one third to one half of HNSCC have clinically positive neck nodes. The objective of the present study was to see whether the progression to a metastatic phenotype is reflected in the distribution of FCM DNA ploidy in node-negative and node-positive HNSCC. The series comprised 200 patients with HNSCC. Tumour samples were obtained from diagnostic biopsies or primary surgery. A multistep preparation method and propidium iodide staining of nuclear DNA content was used for FCM. One hundred and forty one (71%) of the tumours were non-diploid. Only two tumours were hypodiploid (DNA index 0.73 and 0.93, respectively). Ten of the tumours exhibited two non-diploid stem cell lines. The frequency of non-diploidy in node-negative tumours was 65% and in node-positive ones about 80%. The frequency distribution of non-diploid DNA indices clustered in the hypotetraploid region (with a modal value of 1.71-1.74) and did not differ between node-negative and node-positive tumours. The hypothesis that the disposition to metastasis is reflected in the frequency distribution of non-diploid DNA indices could thus not be verified.</p>","PeriodicalId":14452,"journal":{"name":"Invasion & metastasis","volume":"18 4","pages":"184-91"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000024511","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21496150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro invasiveness of human breast cancer cells is promoted by low density lipoprotein receptor-related protein.","authors":"Y Li,&nbsp;N Wood,&nbsp;P Grimsley,&nbsp;D Yellowlees,&nbsp;P K Donnelly","doi":"10.1159/000024517","DOIUrl":"https://doi.org/10.1159/000024517","url":null,"abstract":"<p><p>Low density lipoprotein receptor-related protein/alpha(2)-macroglobulin receptor (LRP) is a surface membrane endocytic receptor, one of whose many functions is the regulation of plasminogen activator-mediated cell migration. LRP is known to have a role in migration and invasion, but its direct involvement has been demonstrated only in non-tumour cells. We investigated six breast cancer cell lines and a normal mammary epithelial cell clone for surface and total cellular LRP expression, and confirmed that its presence corresponds to the ability to invade and migrate in vitro. We showed that LRP in the tumour cell lines is expressed at a wide range of levels: from approximately 300 to approximately 6,300 sites per cell. Four of the breast cancer cell lines expressed LRP at over 1,000 sites/cell and were markedly invasive in our assay, the remainder of the cell lines and the normal clone having far fewer LRP sites and lacking invasive ability. We further showed that the migratory and invasive abilities of a highly invasive breast cancer cell line are both inhibited by receptor-associated protein, a unique LRP ligand which normally has a solely intracellular distribution but which, when added to culture medium, can inhibit all other ligand interactions with this receptor.</p>","PeriodicalId":14452,"journal":{"name":"Invasion & metastasis","volume":"18 5-6","pages":"240-51"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000024517","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21580877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UCN-01, a protein kinase C inhibitor, inhibits endothelial cell proliferation and angiogenic hypoxic response.","authors":"E A Kruger,&nbsp;M V Blagosklonny,&nbsp;S C Dixon,&nbsp;W D Figg","doi":"10.1159/000024514","DOIUrl":"https://doi.org/10.1159/000024514","url":null,"abstract":"<p><p>Angiogenesis is required for tumor formation and growth; inhibition of angiogenesis is a promising new approach in cancer therapy. UCN-01, a protein kinase C (PKC) inhibitor, induces growth arrest and apoptosis in cancer cells and was recently introduced in a phase I clinical trial. We demonstrate that UCN-01, at concentrations lower than those necessary to inhibit cancer cell growth, inhibit proliferation of human endothelial cells in vitro. Moreover, UCN-01, at concentrations as low as 32 nM, prevent microvessel outgrowth from explant cultures of rat aortic rings. Since hypoxia activates hypoxia-inducible factor (HIF-1)-dependent transcription in cancer cells that, in a paracrine fashion, drive tumor angiogenesis, we investigated the effects of UCN-01 on HIF-1-responsive promoter constructs. We report that, in addition to direct inhibitory effects on endothelial cell growth, UCN-01 abrogates hypoxia-mediated transactivation of HIF-1-responsive promoters in a prostate cancer cell line. We conclude that UCN-01, at clinically relevant concentrations, exerts an anti-neovascularization effect by blocking two important steps in vessel formation: (1) the response of cancer cells to hypoxia, and (2) endothelial cell proliferation.</p>","PeriodicalId":14452,"journal":{"name":"Invasion & metastasis","volume":"18 4","pages":"209-18"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000024514","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21496153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clustering of murine lung metastases reflects fractal nonuniformity in regional lung blood flow.","authors":"W S Kendal","doi":"10.1159/000024521","DOIUrl":"https://doi.org/10.1159/000024521","url":null,"abstract":"<p><p>In the experimental metastasis assay certain animals, from groups of similarly treated animals, develop more lung metastases than expected from random chance alone. This clustering of metastases is characterized by a power function relationship, sigma(2) = amu(b), between the variance, sigma(2), and mean, mu, of the numbers of lung metastases per animal (a and b are constants). To determine whether this clustering could be an artifact of experimental metastasis, whether it could be influenced by different experimental conditions, and to attempt to clarify its cause, 22 published data sets from experimental metastasis utilizing 2,145 mice, as well as 8 data sets from spontaneous metastasis utilizing 1,020 mice were analyzed. In these experiments cell cloning, cell-cell fusion, treatment with a protein kinase C inhibitor, treatment with cell adhesion compounds, and transfection with either the ras oncogene, the sialidase gene, or the urokinase sense and antisense genes were used to influence metastasis. They employed 14 different cell lines and 6 different strains of inbred mice. Clustering of metastasis was evident in animals from the spontaneous metastasis assays as well as from the experimental metastasis assays. It was apparent whether mice were injected with tumor cells derived from clones or from cell lines. Clustering was demonstrated within each data set, regardless of the experimental conditions employed. A single variance to mean power function (with a = 2.2 and b = 1.51) characterized the clustering in the 30 data sets. The regional distribution of blood flow through lungs and other organs is nonuniform, exhibiting a fractal symmetry on change of scale. This symmetry implies that the variance of a region's blood flow is related to its mean by the same power function as was observed with metastasis. Indeed, measurements of blood flow from isolated canine lungs yield b = 1.56, similar to the corresponding figure from murine lung metastasis. These findings lend support to the hypothesis that the observed clustering of metastases is a consequence of fractal variations in lung blood flow.</p>","PeriodicalId":14452,"journal":{"name":"Invasion & metastasis","volume":"18 5-6","pages":"285-96"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000024521","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21580843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human metastatic prostate PC3 cell lines degrade bone using matrix metalloproteinases.","authors":"O H Sanchez-Sweatman,&nbsp;F W Orr,&nbsp;G Singh","doi":"10.1159/000024522","DOIUrl":"https://doi.org/10.1159/000024522","url":null,"abstract":"<p><p>Bone metastases are often associated with osteolysis and subsequent pathological fractures. To determine if metastatic human cancer cells can directly degrade non-mineralized and mineralized bone, we used prostate PC3 adenocarcinoma cell lines, which were originally established from skeletal metastases. We show that PC3 cells and their conditioned medium degraded non-mineralized, osteoid-like radiolabelled extracellular matrices from human Saos2 and U2OS osteoblast-like cells. These cells also directly degraded mineralized bone by inducing (45)Ca release from rat fetal calvariae and forming resorption pits on bone slices, an effect increased by transforming growth factor-beta(1). A role for matrix metalloproteinases in degradation was shown by: (1) stimulation by the phorbol ester TPA of PC3-induced matrix degradation and release of matrix metalloproteinase activity; (2) abrogation of matrix degradation by 1,10-phenanthroline, a metalloproteinase inhibitor, and (3) degradation of purified type I collagen by PC3 cells and their conditioned medium. We demonstrate that human prostate cancer cells can directly degrade bone-related matrices and that matrix metalloproteinases have a role in this process.</p>","PeriodicalId":14452,"journal":{"name":"Invasion & metastasis","volume":"18 5-6","pages":"297-305"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000024522","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21580845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metastatic dissemination of human ovarian epithelial carcinoma is promoted by alpha2beta1-integrin-mediated interaction with type I collagen.","authors":"D A Fishman,&nbsp;A Kearns,&nbsp;K Chilukuri,&nbsp;L M Bafetti,&nbsp;E A O'Toole,&nbsp;J Georgacopoulos,&nbsp;M J Ravosa,&nbsp;M S Stack","doi":"10.1159/000024495","DOIUrl":"https://doi.org/10.1159/000024495","url":null,"abstract":"<p><p>Metastatic dissemination of epithelial ovarian carcinoma is thought to be mediated via tumor cell exfoliation into the peritoneal cavity, followed by adhesion to and invasion through the mesothelium which overlies the contents of the peritoneal cavity. In this study, we have utilized short-term primary cultures to analyze the effect of specific extracellular matrix proteins on properties of human ovarian epithelial carcinoma cells which contribute to the invasive phenotype. Analysis of cell:matrix adhesive profiles indicated that ovarian carcinoma cells adhere preferentially to type I collagen. Immunoprecipitation analyses demonstrated the presence of the collagen-binding alpha2beta1 integrin in biotin-labeled ovarian carcinoma cell membranes, and cellular adhesion was inhibited by blocking antibodies directed against the alpha2 and beta1 integrin subunits. The alpha2beta1-binding peptide Asp-Gly-Glu-Ala (DGEA) was also moderately effective at blocking adhesion to collagen relative to the control peptide Ala-Gly-Glu-Ala (AGEA). Analysis of cell motility on protein-coated colloidal gold coverslips demonstrated that ovarian carcinoma cells migrate preferentially on type I collagen coated surfaces. Type I collagen promoted migration in a concentration-dependent, saturable manner, with maximal migration observed at a collagen-coating concentration of 50 microg/ml. Migration on collagen was inhibited by antibodies directed against the alpha2 and beta1 integrin subunits and by DGEA peptide, providing evidence for the role of the alpha2beta1 integrin in ovarian carcinoma cell motility. Culturing ovarian carcinoma cells on type I collagen gels led to a significant increase in conversion of the matrix metalloproteinase 2 zymogen to the 66-kD form, suggesting that adhesion to collagen also influences matrix-degrading proteinases. These data suggest that alpha2beta1-integrin-mediated interaction of ovarian carcinoma cells with type I collagen, a protein prevalent both in the mesothelial extracellular matrix and in the peritoneal cavity of ovarian carcinoma patients, may function on multiple levels to promote metastatic dissemination of ovarian carcinoma cells.</p>","PeriodicalId":14452,"journal":{"name":"Invasion & metastasis","volume":"18 1","pages":"15-26"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000024495","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21078268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accumulation of genetic alterations in brain metastases of sporadic breast carcinomas is associated with reduced survival after metastasis.","authors":"M Hampl,&nbsp;J A Hampl,&nbsp;P Schwarz,&nbsp;S Frank,&nbsp;M Hahn,&nbsp;G Schackert,&nbsp;H D Saeger,&nbsp;H K Schackert","doi":"10.1159/000024501","DOIUrl":"https://doi.org/10.1159/000024501","url":null,"abstract":"<p><p>Tumor progression is characterized by stepwise accumulation of genetic alterations. To identify alterations associated with breast cancer metastasis, an analysis of comparative loss of heterozygosity (LOH) was performed on 38 primary sporadic breast carcinomas and 16 distant metastases. Two loci at 5q21 and 18q21 were chosen because of their reported increased deletion frequency in metastatic tumors. LOH at 17q21, 13q12-13, 17p13.1 and 11q22-23 was analyzed to determine whether there is a specific involvement of these breast cancer-associated gene loci in the metastatic process. Our data show that distant metastases are characterized by markedly increased LOH frequency at all loci examined. In both gene locus groups, significantly more distant metastases are affected by combined LOH. Furthermore, a significantly reduced postmetastatic survival time has been observed in patients with brain metastases affected by synchronous allelic loss at the four breast cancer-associated gene loci. Our results suggest that cumulative LOH of breast cancer-related gene loci is associated with a more aggressive phenotype of metastatic breast tumors.</p>","PeriodicalId":14452,"journal":{"name":"Invasion & metastasis","volume":"18 2","pages":"81-95"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000024501","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21233472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue-specific posttranscriptional downregulation of expression of the S100A4(mts1) gene in transgenic animals.","authors":"N Ambartsumian,&nbsp;J Klingelhöfer,&nbsp;M Grigorian,&nbsp;O Karlstrøm,&nbsp;N Sidenius,&nbsp;G Georgiev,&nbsp;E Lukanidin","doi":"10.1159/000024502","DOIUrl":"https://doi.org/10.1159/000024502","url":null,"abstract":"<p><p>The S100A4(mts1) is a gene associated with generation of metastatic disease. In order to analyze the consequences of alteration of the pattern of expression of the S100A4(mts1) gene we obtained strains of transgenic mice bearing the S100A4(mts1) gene under the control of a ubiquitous and constitutive 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) gene promoter. In transgenic animals the expression of the transgene RNA was detected in all organs, but only some of the organs showed elevated levels of the protein. Expression of the S100A4(Mts1) protein was downregulated in the organs that normally do not express the gene in the wild-type animal. The transgene RNA is detected in the polysomes indicating that it could be translated into the S100A4(Mts1) protein. The specificity of the S100A4(Mts1) protein expression is determined by a complex mechanism including regulation of translation and/or posttranslational degradation.</p>","PeriodicalId":14452,"journal":{"name":"Invasion & metastasis","volume":"18 2","pages":"96-104"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000024502","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21233473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}