Document Detail


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.
MedLine Citation:
PMID:  12479696     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Brendan P Keegan; Vincent A Memoli; William G North
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular cancer therapeutics     Volume:  1     ISSN:  1535-7163     ISO Abbreviation:  Mol. Cancer Ther.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-12-13     Completed Date:  2003-05-15     Revised Date:  2013-08-14    
Medline Journal Info:
Nlm Unique ID:  101132535     Medline TA:  Mol Cancer Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1153-9     Citation Subset:  IM    
Affiliation:
Departments of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
CA 19613/CA/NCI NIH HHS; CA 23108/CA/NCI NIH HHS; DK 07508/DK/NIDDK NIH HHS; P30 CA023108/CA/NCI NIH HHS; R01 CA019613/CA/NCI NIH HHS; T32 DK007508/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
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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