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Regulated expression of exon v6 containing isoforms of CD44 in man: downregulation during malignant transformation of tumors of squamocellular origin.
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MedLine Citation:
PMID:  8320265     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CD44 is a family of glycoproteins involved in cell-cell and cell-matrix interactions. In addition to the major 90-kD form present on most hematopoietic cells, larger 140-230 kD forms are found on keratinocytes and carcinoma cell lines. These bigger isoforms of CD44 arise by alternative splicing that results in insertion of one or more of the "variant" exons into the extracellular part of the 90-kD constant form of the molecule. In rat, v6 (variant exon v6) containing form of CD44 confers metastatic potential to carcinoma cells, and therefore, it is of interest to study the distribution of this isoform in humans. We raised antibodies against a synthetic peptide containing a sequence encoded by the exon v6. A mAb thus obtained (designated Var3.1) strongly reacted with the plasma membranes of squamous cells in upper layers of skin and tonsil surface epithelia. Weaker staining was seen in germinal centers, vascular endothelia and enterocytes. Exon v6 containing forms of CD44 (CD44v6) were absent from tissue leukocytes and connective tissue components. In comparison, Hermes-3 epitope (on the constant part) containing forms of CD44 were preferentially localized in basal layers of epithelia, present on the surface on most leukocytes and connective tissue cells, and undetectable on the luminal surface of high endothelial venules. In benign neoplasms, epithelial cells stained with mAb Var3.1 like in normal tissues. In contrast, immunostaining of 30 squamous carcinoma specimens (both primary and metastatic lesions) revealed that malignant transformation resulted in downregulation or disappearance of Var3.1 epitope, but in majority of cases, not in diminished synthesis of the Hermes-3 epitope. Biochemical analyses showed that mAb Var3.1 recognized two major forms of CD44 (220 and 300 kD). In conclusion, epitopes on exon v6 and constant part of CD44 are differentially synthesized and regulated during normal and malignant growth of cells in man.
Authors:
M Salmi; K Grön-Virta; P Sointu; R Grenman; H Kalimo; S Jalkanen
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of cell biology     Volume:  122     ISSN:  0021-9525     ISO Abbreviation:  J. Cell Biol.     Publication Date:  1993 Jul 
Date Detail:
Created Date:  1993-08-03     Completed Date:  1993-08-03     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0375356     Medline TA:  J Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  431-42     Citation Subset:  IM    
Affiliation:
National Public Health Institute, MediCity Unit, Turku, Finland.
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MeSH Terms
Descriptor/Qualifier:
Adult
Amino Acid Sequence
Antibodies, Monoclonal
Base Sequence
Carcinoma, Squamous Cell / genetics,  immunology*
Cell Line, Transformed
Cell Transformation, Neoplastic*
Connective Tissue / immunology
Connective Tissue Cells
Down-Regulation
Exons*
Head and Neck Neoplasms / genetics,  immunology
Humans
Leukocytes / immunology
Lymphocytes / immunology
Molecular Sequence Data
Papilloma / genetics,  immunology*
Receptors, Lymphocyte Homing / analysis,  chemistry,  genetics*,  immunology
Solubility
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Receptors, Lymphocyte Homing
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): J Cell Biol
ISSN: 0021-9525
ISSN: 1540-8140
Publisher: The Rockefeller University Press
Article Information
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Print publication date: Day: 2 Month: 7 Year: 1993
Volume: 122 Issue: 2
First Page: 431 Last Page: 442
ID: 2119652
Publisher Id: 93308147
PubMed Id: 8320265

Regulated expression of exon v6 containing isoforms of CD44 in man: downregulation during malignant transformation of tumors of squamocellular origin


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