Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: ANGIOGENESIS ; INHIBITION ; tumor ; METASTASIS
    Type of Publication: Patent
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: RECEPTOR ; ANGIOGENESIS ; CANCER ; CANCER CELLS ; CELLS ; EXPRESSION ; GROWTH ; tumor ; TUMOR-CELLS ; carcinoma ; ENDOTHELIAL GROWTH-FACTOR ; Germany ; human ; PATHWAY ; SYSTEM ; PROTEIN ; TISSUE ; TUMORS ; LINES ; PATIENT ; COMPLEX ; COMPLEXES ; MARKER ; prognosis ; TISSUES ; BINDING ; CELL-LINES ; SIGNAL ; NERVOUS-SYSTEM ; PROGRESSION ; ovarian cancer ; OVARIAN-CANCER ; CELL-LINE ; FUSION ; LINE ; CANCER-CELLS ; ADHESION ; INTEGRIN ; CARCINOMAS ; RT-PCR ; L1 ; NEURITE OUTGROWTH ; ADHESION MOLECULE ; L1 adhesion molecule ; ovarian carcinoma ; OVEREXPRESSION ; cell lines ; TUMOR CELLS ; PERMEABILITY ; RE ; TUMOR-GROWTH ; cell adhesion ; LEVEL ; TUMOR-CELL ; ADHESION MOLECULE L1 ; OVARIAN CARCINOMAS ; function ; SIGNALS ; OVARIAN ; VARIETIES ; VASCULAR-PERMEABILITY ; heterophilic binding ; mesothelial cells ; MOUSE LEUKOCYTES ; neuropilin-1 ; SEMAPHORIN-III
    Abstract: The progression of ovarian cancer is driven by a variety of cellular factors that are incompletely understood. Binding of tumor cells to normal cells and to soluble factors influence tumor growth, angiogenesis and the stimulation of vascular permeability leading to ascites production. L1 adhesion molecule is overexpressed in ovarian carcinoma and is associated with bad prognosis. One receptor for L1 is Neuropilin-1 (NRP-1) that is also known as a receptor for VEGF(165). In the nervous system a complex of NRP-1 and L1 transmits signals by the neurorepellant Sem3A that is critical for the control of neurite outgrowth. NRP-1 has also been detected in human carcinomas but its function remains unknown. Here, we have examined NRP-1 expression in ovarian carcinoma cell lines and tissue. We report that little NRP-1 protein was detected in primary ovarian carcinoma tissues or established cell lines although mRNA for soluble and transmembrane NRP-1 were detected by RT-PCR. Instead, we observed strong expression of NRP-1 in mesothelial cells, which form the lining of the peritoneum. NRP-1 could serve as an isolation marker for primary mesothelial cells present in ascites fluid. We demonstrate that ovarian cancer cells expressing L1 can bind to NRP-1 overexpressing cells and mesothelial cells. Likewise, soluble L1 isolated from ascites of patients or produced as a fusion protein could bind to NRP-1 overexpressing cells and a direct interaction was demonstrated at the protein level. These findings suggest that L1 can support the binding of ovarian carcinoma cells to mesothelial cells via NRP-1. The L1-NRP-1 binding pathway could contribute to the growth of ovarian carcinomas and to reciprocal signalling between mesothelial cells and tumors. (c) 2005 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 16377081
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: CELLS ; EXPRESSION ; GROWTH ; tumor ; carcinoma ; Germany ; KINASE ; PATHWAY ; GENE ; GENE-EXPRESSION ; PROTEIN ; PROTEINS ; TISSUE ; TUMORS ; LINES ; MICE ; gene transfer ; GENE-TRANSFER ; ACTIVATION ; prognosis ; CELL-LINES ; VARIANTS ; MOLECULE ; PROGRESSION ; gene expression ; TUMOR PROGRESSION ; METASTASIS ; LINE ; EXTRACELLULAR-MATRIX ; BETA ; ADHESION ; MIGRATION ; INTEGRIN ; CARCINOMAS ; L1 ; ADHESION MOLECULE ; ovarian carcinoma ; OVEREXPRESSION ; cell lines ; CELL-MIGRATION ; MORPHOGENESIS ; MATRIX ; RE ; TUMOR-GROWTH ; extracellular matrix ; cell adhesion ; cell migration ; CANCER PROGRESSION ; PROFILES ; ERK ; EPITHELIUM ; ADHESION MOLECULE L1 ; CD171 ; CUTANEOUS MALIGNANT-MELANOMA ; VITRONECTIN
    Abstract: L1 is a neural cell adhesion molecule involved in cell migration, axon growth and guidance. Recent data have shown that L1 is overexpressed in ovarian and endometrial tumors and is associated with bad prognosis. How L1 promotes tumor progression is presently unknown. Here we show that L1 expression is predominantly confined to the invasive front of ovarian carcinomas. Overexpression of L1 in carcinoma cell lines by adenovirus-mediated gene transfer enhanced the haptotactic cell migration on extracellular matrix proteins. Expression of L1 augmented tumor growth of carcinomas xenografted in nonobese diabetic/severe combined immunodeficient mice (NOD/SCID). A recent report has demonstrated L1-dependent upregulation of P3 integrin involving activation of the extracellular signal-regulated kinase (erk) pathway. We find that L1 and P3 integrin are not coexpressed in ovarian carcinoma tissues. Overexpression of L1 did not upregulate P3 integrin in ovarian carcinoma cell lines but could do so in HEK293 cells. Our results suggest that L1 could drive progression by enhancing cell migration and tumor growth but that L1 dependent and erk-regulated gene expression requires cell-type specific elements. © 2005 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 15704102
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: CANCER ; CELLS ; EXPRESSION ; tumor ; TUMOR-CELLS ; carcinoma ; CELL ; Germany ; INHIBITION ; SYSTEM ; TUMORS ; LINES ; BINDING ; SUSCEPTIBILITY ; antibodies ; CELL-LINE ; ADHESION ; TUMOR CELLS ; neuroblastoma ; TUMOR-CELL ; SULFATE ; NATURAL-KILLER
    Abstract: Expression of the neural cell adhesion molecule (NCAM) on malignant cells of neuroendocrine, epithelial and hematopoeitic origin has been reported, but its role for tumor cell recognition by the immune system remained uncertain so far. We have studied the cytotoxicity of the natural killer (NK) cell line NK92 and polyclonal NK cells from different donors, against NCAM-deficient and NCAM-transfected tumors. While the pancreatic carcinoma PANC-1 and the glioblastoma T98G showed no enhanced susceptibility to NK lysis after NCAM transfection, de novo NCAM expression in HeLa cervical carcinoma, SHEP neuroblastoma and the multiple myeloma lines RPMI-8226 and LP-1 was associated with significantly decreased lysis by NK cells. Binding of an NCAM-specific monoclonal antibody to NCAM-positive target cells was able to reverse the reduced lysis susceptibility. Conjugate formation of NCAM-expressing tumor cells with NK cells was blocked and could be restored by anti-NCAM. NK cell-expressed NCAM molecules which might engage in homotypic cis- or trans-interactions had no apparent inhibitory function. The known cis-ligands of NCAM, heparan sulfate proteoglycan and L1-CAM, were also not directly involved in NK inhibition. ICAM-1 mRNA and cell surface expression was downmodulated in NCAM-transfected HeLa cells. ICAM-1 is involved in killer cell immune synapse formation. Its downmodulation may therefore contribute to the reduced lysis of NCAM-expressing target cells. We conclude that aberrant expression of NCAM on tumor cells of different histogenetic origin can lead to inhibition of target cell recognition and lysis by NK cells. (c) 2007 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 17294447
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: CELLS ; EXPRESSION ; INVASION ; tumor ; TUMOR-CELLS ; carcinoma ; CELL ; Germany ; DENSITY ; ENZYMES ; PROTEIN ; PROTEINS ; cell line ; TISSUE ; LINES ; PATIENT ; MARKER ; prognosis ; CELL-LINES ; MOLECULE ; BREAST-CANCER ; NO ; PROGRESSION ; TUMOR PROGRESSION ; CELL-LINE ; LINE ; ADHESION ; CELL-ADHESION ; CARCINOMAS ; P-SELECTIN ; ADHESION MOLECULE ; POOR-PROGNOSIS ; cell lines ; TUMOR CELLS ; CD24 ; ORIGIN ; ONCOLOGY ; RE ; VESICLES ; secretion ; INDEPENDENT PROGNOSTIC MARKER ; cell adhesion ; TUMOR TISSUE ; ENZYME ; analysis ; methods ; TUMOR-CELL ; OVARIAN CARCINOMAS ; USA ; correlation ; EpCAM ; B-LYMPHOCYTES ; OVARIAN ; exosome ; exosomes ; FRACTIONATION ; OVARIAN-CARCINOMA ; ovarian carcinoma cells ; malignant ascites ; PRE-B
    Abstract: Objective. CD24 is an established marker for poor prognosis in ovarian and other carci nomas. Acquisition of cytoplasmic CD24, as opposed to membranous expression, has been correlated with a higher invasiveness of tumor cells. Exosomes are small vesicles of endosomal origin that are often secreted by tumor cells. Given the emerging role of exosomes in tumor progression, we investigated whether cytoplasmic CD24 expression is correlated with the secretion of CD24 in exosomes. Methods. We used CD24 transfected carcinoma cell lines, ovarian carcinoma cell lines and malignant ascites fluid of ovarian carcinoma patients. Exosomes were isolated via ultracentrifugation and sucrose density fractionation and subsequently examined by Western blot analysis and gelatine zymography. In tissue sections CD24 was detected by immunohistochemical staining. Results. We show that CD24 is released by transfected as well as endogenously expressing cells in vesicles that represent exosomes. CD24 was also identified in exosomes isolated from ascites fluid of ovarian carcinoma patients. In 16 ovarian carcinomas analyzed no correlation between CD24 in tumor tissue sections and the appearance of CD24 in exosomes was detected. Furthermore, we provide evidence that the epithelial cell adhesion molecule (EpCAM), known to be overexpressed in ovarian carcinomas, is secreted in exosomes. The ascites exosomes contain gelatinolytic enzymes. Conclusions. Our study identifies CD24 and EpCAM as cargo proteins of exosomes of cultured cell lines and malignant ascites. The exosome-associated proteolytic activity in the tumor vicinity might augment tumor invasion into the stroma. (c) 2007 Elsevier Inc. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 17900673
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Keywords: APOPTOSIS ; CANCER ; CELLS ; EXPRESSION ; INVASION ; tumor ; carcinoma ; CELL ; Germany ; RNA ; cell line ; LINES ; ACTIVATION ; INDUCTION ; colon ; BINDING ; CELL-LINES ; PHOSPHORYLATION ; treatment ; MOLECULE ; PROGRESSION ; resistance ; CARCINOMA CELLS ; INDUCED APOPTOSIS ; METASTASIS ; CELL-LINE ; chemotherapy ; LINE ; CARCINOMA-CELLS ; ADHESION ; MIGRATION ; PHENOTYPE ; CARCINOMAS ; L1 ; MALIGNANT-MELANOMA ; SELECTION ; ADHESION MOLECULE ; L1 adhesion molecule ; cell lines ; Bcl-2 ; HYPOXIA ; chemoresistance ; ENDOMETRIAL ; RE ; TUMOR-GROWTH ; INTERFERENCE ; RNA INTERFERENCE ; LEADS ; methods ; ADHESION MOLECULE L1 ; DEPLETION ; OVARIAN ; ovarian carcinoma cells ; apoptosis protection
    Abstract: Objective. Apoptosis resistance is a hallmark of cancer progression, a phenomenon frequently observed in ovarian carcinoma. We reported previously, that L1 adhesion molecule (CD171) is overexpressed in ovarian and endometrial carcinomas and that L1 expression is a predictor of poor outcome. We investigated a possible role of L1 in apoptosis resistance. Methods. We used L1 transfectants and ovarian carcinoma cell lines and induced apoptosis by different stimuli such as C2-ceramide, staurosporine, cisplatin or hypoxia. Results. We found that cells expressing L1 are more resistant against apoptosis. In HEK293 cells, L1-expresssion leads to a sustained ERK, FAK and PAK phosphorylation. Soluble L1 only partially rescued HEK-293 cells from apoptosis. Treatment with apoptotic stimuli upregulated the anti-apoptotic molecule Bcl-2 to a greater extend in HEK293 cells expressing L1. In the ovarian carcinoma cell line OVMz, the depletion of L1 by RNA interference sensitized cells for apoptosis induction. No changes in activation of ERK or FAK were observed after L1 knockdown. The selection of m130 ovarian carcinoma or SW707 colon carcinoma cells with cisplatin leads to upregulated expression of L1. Conclusions. Our results suggest a link between L1 expression and chemoresistance of ovarian carcinomas. Upregulation of L1 after cisplatin treatment might indicate a more malignant tumor phenotype given the established role of L1 in cell motility and invasion. (c) 2006 Elsevier Inc. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 17030349
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Keywords: CELLS ; EXPRESSION ; GROWTH ; tumor ; carcinoma ; CELL ; Germany ; human ; THERAPY ; tumor growth ; SYSTEM ; GENE ; GENE-EXPRESSION ; GENES ; PROTEIN ; PROTEINS ; transcription ; TUMORS ; MICE ; ACTIVATION ; TRANSCRIPTION FACTOR ; prognosis ; INDUCTION ; BINDING ; BIOLOGY ; MOLECULAR-BIOLOGY ; MOLECULE ; antibodies ; TARGET ; NERVOUS-SYSTEM ; gene expression ; METASTASIS ; genetics ; IMMUNODEFICIENT MICE ; MIGRATION ; ONCOGENE ; MALIGNANT-MELANOMA ; NEURITE OUTGROWTH ; ADHESION MOLECULE ; CELL-ADHESION MOLECULE ; OVEREXPRESSION ; CELL-MIGRATION ; heredity ; signaling ; molecular biology ; molecular ; ONCOLOGY ; RE ; PATTERN ; TUMOR-GROWTH ; INTERFERENCE ; THERAPIES ; ACTIVATED PROTEIN-KINASES ; cell migration ; OVARIAN CARCINOMAS ; MOTILITY ; ENGLAND ; cathepsin B ; L1 CD171 ; MELANOMA PROGRESSION ; therapeutic antibodies
    Abstract: L1 cell adhesion molecule (L1-CAM) is a transmembrane cell adhesion molecule involved in cell migration and axon guidance in the developing nervous system. L1 is also overexpressed in ovarian and endometrial carcinomas and is associated with a bad prognosis. In carcinoma cell lines, L1 overexpression augments cell motility, tumor growth in mice and induces expression of Erk-dependent genes. Here, we show that a mutation in the cytoplasmic portion of L1 (T1247A, S1248A) abrogates Erk activation, blocks cell migration on extracellular matrix proteins and did not augment tumor growth in non-obese diabetic/severe combined immuno-deficient mice. In cells expressing mutant L1, the induction of Erk-dependent genes such as beta 3-integrin, cathepsin-B and several transcription factors is eliminated and the invasive phenotype is abrogated. L1 antibodies showed similar effects. They prevented Erk activation and interfered with the Erk-dependent gene expression pattern. These findings provide a rationale for the mode of action of L1 antibodies and suggest that interference with L1 function could become a valuable target for therapy
    Type of Publication: Journal article published
    PubMed ID: 17952127
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...