Document Detail


Retinoid status and the control of keratin expression and adhesion during the histogenesis of squamous metaplasia of tracheal epithelium.
MedLine Citation:
PMID:  1384955     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We induced vitamin A depletion to define early and late changes during the histogenesis of squamous metaplasia of hamster tracheal epithelium. An early change is the "minimal morphological change" (MMC), in which the mucociliary epithelium is separated from the basement membrane by a continuous layer of basal cells. Immunohistochemistry showed an exclusive localization of the keratins K5 and K14 in basal cells of normal and MMC epithelia. At the MMC stage no staining was observed above the basal layer with antibodies to K5, but upon progression of the lesion to a squamous focus all cells from basal to terminally differentiated were positive for K5 and K14. In contrast, when we used antibodies to the keratins K6 or K13 all cells were negative in the normal epithelium and in the MMC epithelium. Successive layers of suprabasal squamous cells found in squamous metaplasia failed to express normal epidermal differentiation marker keratins K1 and K10 but expressed the proliferation marker keratin K6 and the internal stratified epithelium keratin K13, not normally found in the epidermis or in the trachea. Hamster tracheal epithelial cells could be maintained in culture in serum-free medium for at least 4 weeks in the presence of retinoic acid (RA). In non-RA-containing medium, cells from vitamin A-deficient hamsters showed markedly reduced growth and an increase in the expression of keratins K5, K6, K13, and K14. Since our previous work had implicated retinoids in the control of cell adhesiveness, we were interested to find out whether changes in cell adhesion occur in vitamin A-deficient hamster tracheal epithelial cells, compared to normal cells. Functional assays demonstrated that hamster tracheal epithelial cells, obtained from non-RA-treated tracheas or maintained in culture, displayed reduced attachment to laminin, compared to RA-treated cells. Immunofluorescence studies did not show a decrease either in the alpha 6 integrin subunit, which was localized in the basal aspect of basal cells, or in basement membrane laminin. However, the expression of laminin-binding protein 37 decreased as the epithelium changed from pseudostratified to stratified. Therefore, a coordinated pattern of changes in keratin gene expression, as well as in the expression of laminin-binding protein 37, the precursor to the cell surface laminin receptor 67LR, and in adhesive properties takes place in tracheal epithelium when its phenotype changes from mucociliary to the preneoplastic stage of squamous metaplasia.
Authors:
F Lancillotti; N Darwiche; G Celli; L M De Luca
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cancer research     Volume:  52     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1992 Nov 
Date Detail:
Created Date:  1992-12-09     Completed Date:  1992-12-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  6144-52     Citation Subset:  IM    
Affiliation:
Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Antibodies
Blotting, Western
Cell Adhesion / physiology
Cell Adhesion Molecules / analysis,  physiology*
Cells, Cultured
Cricetinae
Epithelium / pathology
Fibroblasts / pathology
Immunohistochemistry
Keratins / analysis,  physiology*
Laminin / analysis,  physiology
Male
Mesocricetus
Metaplasia / etiology
Molecular Sequence Data
Protein Binding
Trachea / pathology*
Tretinoin / pharmacology*
Vitamin A Deficiency / physiopathology*
Chemical
Reg. No./Substance:
0/Antibodies; 0/Cell Adhesion Molecules; 0/Laminin; 302-79-4/Tretinoin; 68238-35-7/Keratins

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