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  • 1
    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
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  • 2
    Keywords: EXPRESSION ; tumor ; carcinoma ; Germany ; human ; IN-VIVO ; LUNG ; THERAPY ; VIVO ; DIAGNOSIS ; SYSTEM ; MONOCLONAL-ANTIBODY ; TISSUE ; TUMORS ; LINES ; kidney ; MARKER ; colon ; TISSUES ; BINDING ; CELL-LINES ; BREAST ; antibodies ; antibody ; NERVOUS-SYSTEM ; PROGRESSION ; immunohistochemistry ; METASTASIS ; CERVIX ; CELL-LINE ; LINE ; MELANOMA ; ADHESION ; CELL-ADHESION ; MIGRATION ; MONOCLONAL-ANTIBODIES ; BENIGN ; INTEGRIN ; CARCINOMAS ; adenocarcinoma ; ADENOCARCINOMAS ; L1 ; MALIGNANT-MELANOMA ; ADHESION MOLECULE ; CELL-ADHESION MOLECULE ; cell lines ; LUNG-CARCINOMA ; DOMAINS ; ADULTS ; ENDOMETRIAL ; RE ; cell adhesion ; SUBTYPES ; CD171 ; lung carcinoma ; in vivo ; PREDICTOR ; RENAL-CARCINOMA ; OVARIAN ; molecular marker ; pediatric ; nongynecological tumors ; OVARIAN-CARCINOMA CELLS ; tumors of female genital tract
    Abstract: L1 cell adhesion molecule (CD171) represents a strongly unfavorable prognostic biomarker for ovarian and endometrial carcinomas. Here we carried out an immunohistochemical survey of L1 expression in normal adults and in a broad range of benign and malignant tumors using monoclonal antibody L1-11A and the novel monoclonal antibody L1-14.10. In normal tissues, L1 was expressed in the collecting tubules of adult tissues and pediatric kidney and in peripheral nerve bundles. In tumors of the female genital tract, L 1 was detected in adenocarcinomas of the cervix and fallopian tubes, in addition to ovarian and endometrial carcinomas. Nongynecological tumors expressing L1 comprised malignant melanoma, colon adenocarcinoma positive to chromogranin, clear-cell adenocarcinoma of the urinary bladder, pheochromocytoma, small cell lung carcinoma, and tumors of the nervous system. L1 was absent in breast carcinoma, gastrointestinal tract carcinomas, gastrointestinal carcinoids, renal clear-cell carcinomas, prostate adenocarcinomas, and mesotheliomas. Surprisingly, L1 expression in established breast and renal carcinoma cell lines was not a predictor for its presence in these human tumors in vivo. Our results suggest that L1 expression in tumors is not ubiquitous but restricted to certain subtypes and may be a helpful molecular marker for differential diagnosis and target for antibody-based therapy. (c) 2006 Elsevier Inc. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 16867862
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    Keywords: APOPTOSIS ; CANCER ; CELLS ; GROWTH ; IN-VITRO ; tumor ; carcinoma ; Germany ; human ; DEATH ; DISEASE ; GENE-EXPRESSION ; TUMORS ; LINES ; MICE ; colon ; PROGRESSION ; OVARIAN-CANCER ; TUMOR PROGRESSION ; METASTASIS ; NUDE-MICE ; MIGRATION ; L1 ; SELECTION ; OVEREXPRESSION ; neuroblastoma ; CHCE7 ; RENAL-CARCINOMA
    Abstract: The L1 cell adhesion molecule is implicated in the control of proliferation, migration, and invasion of several tumor cell types in vitro. Recently, L1 overexpression was found to correlate with tumor progression of ovarian carcinoma, one of the most common causes of cancer-related deaths in gynecologic malignant diseases. To evaluate L1 as a potential target for ovarian cancer therapy, we investigated the effects of anti-L1 monoclonal antibodies (chCE7 and L1-11A) on proliferation and migration of L1-positive human SKOV3ip ovarian carcinoma cells in vitro and the therapeutic efficacy of L1-11A against i.p. SKOV3ip tumor growth in nude mice. In vitro, both anti-L1 antibodies efficiently inhibited the proliferation of SKOV3ip cells as well as other L1-expressing tumor cell lines (renal carcinoma, neuroblastoma, and colon carcinoma). On two cell lines, hyper-cross-linking of L1-11A with a secondary antibody was necessary for significant inhibition of proliferation, indicating that cross-linking of L1 is required for the antiproliferative effect. L1-negative prostate carcinoma cells were not influenced by antibody treatment. Biweekly treatment of ovarian carcinoma-bearing mice with L1-11A led to a dose-dependent and significant reduction of tumor burden (up to -63.5%) and ascites formation (up to -75%). This effect was associated with reduced proliferation within the tumors. L1-directed antibody-based inhibition of peritoneal growth and dissemination of human ovarian carcinoma cells represents important proof-of-principle for the development of a new therapy against one of the leading gynecologic malignant diseases
    Type of Publication: Journal article published
    PubMed ID: 16424028
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