| Targeting the neurophysin-related cell surface antigen on small cell lung cancer cells using a monoclonal antibody against the glycopeptide region (MAG-1) of provasopressin. | |
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MedLine Citation:
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PMID: 12479696 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The vasopressin (VP) gene is largely expressed in hypothalamic neurons, where the resultant pro-VP protein is enzymatically cleaved into its peptide hormone components, which include the neuropeptide VP, VP-associated neurophysin, and VP-associated glycopeptide (VAG). Small cell lung cancer (SCLC) tumors also express the VP gene, but the tumor pro-VP protein can remain intact and localize to the cell surface membrane. Previous studies have shown that polyclonal antibodies directed against different regions of the pro-VP protein bind specifically to the surface of cultured SCLC cells and recognize proteins of approximately 20 and approximately 40 kDa in cultured SCLC whole-cell lysate. Thus, these proteins have been designated neurophysin-related cell surface antigen (NRSA). A monoclonal antibody (mAb) designated MAG-1 was raised in this laboratory using a synthetic peptide representing the COOH-terminal sequence of VAG. The MAG-1 mAb recognizes NRSA in SCLC cell and tissue lysates by Western analysis, whereas immunofluorescent cytometric and microscopic analyses indicate that MAG-1 reacts specifically with NRSA on the surface of viable SCLC cells of both the classical and the variant subtype. Immunohistochemical analysis demonstrates that MAG-1 reacts with human SCLC tumor, but not with normal pulmonary epithelial cells in lung tissue. Additionally, a MAG-1 Fab fragment was generated that was also able to recognize NRSA. This is the first study to demonstrate that a mAb directed to the VAG region of the pro-VP protein has the potential for development into an in vivo diagnostic and therapeutic tool that targets plasma membrane-incorporated NRSA. |
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Authors:
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Brendan P Keegan; Vincent A Memoli; William G North |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Molecular cancer therapeutics Volume: 1 ISSN: 1535-7163 ISO Abbreviation: Mol. Cancer Ther. Publication Date: 2002 Nov |
Date Detail:
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Created Date: 2002-12-13 Completed Date: 2003-05-15 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 101132535 Medline TA: Mol Cancer Ther Country: United States |
Other Details:
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Languages: eng Pagination: 1153-9 Citation Subset: IM |
Affiliation:
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Departments of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Monoclonal / diagnostic use* Antigens, Neoplasm / analysis* Antigens, Surface / analysis* Arginine Vasopressin* Blotting, Western Carcinoma, Small Cell / immunology* Glycoproteins / immunology* Immunoenzyme Techniques Lung / metabolism, pathology Lung Neoplasms / immunology* Mice Mice, Inbred BALB C Neurophysins / immunology* Oxytocin* Protein Precursors / immunology* Reverse Transcriptase Polymerase Chain Reaction Tumor Cells, Cultured Vasopressins / immunology* |
| Grant Support | |
ID/Acronym/Agency:
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CA 19613/CA/NCI NIH HHS; CA 23108/CA/NCI NIH HHS; DK 07508/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Antigens, Neoplasm; 0/Antigens, Surface; 0/Glycoproteins; 0/Neurophysins; 0/Protein Precursors; 11000-17-2/Vasopressins; 113-79-1/Arginine Vasopressin; 50-56-6/Oxytocin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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