Expression of gap junction proteins (connexin 26, 30, 32, 43) in normal mucosa, hyperkeratosis and carcinoma of the human larynx.
BACKGROUND
Gap junction proteins (connexins = Cx) form transmembrane channels and mediate the transfer of small molecules and ions between the cytoplasm of adjacent cells. Most tissues express several Cx isoforms. The precise combination might play an important role in the maintenance of cell differentiation. Human carcinogenesis is accompanied by aberrant expression and function of Cx. While the larynx is a target organ for many tumor promoters, no data on Cx expression in laryngeal mucosa are available. The goal of the study was to observe the expression of different Cx (Cx26, -30, -32 and -43) in the normal mucosa, hyperkeratoses and carcinomas of the human larynx.


METHODS
The immunofluorescence method was performed in normal (n = 7) and dysplastic (n = 6) laryngeal mucosa and in squamous cell carcinoma (n = 7) using affinity-purified polyclonal rabbit antibodies against the 4 Cx isoforms and FITC-conjugated secondary antibodies.


RESULTS
The immunofluorescence staining of the normal human vocal fold's epithelium showed the expression of Cx26 and Cx30 in the parabasal and intermediate layers, whereas Cx43 was localized in the basal, parabasal and lower intermediate layers. Cx epitopes could not be found in the upper layers. The precanceroses showed a similar expression of the Cx compared to normal laryngeal epithelium. Due to the higher degree of staining observed in dysplastic specimens, a hyperexpression of Cx26, -30 and -43 could be assumed. The squamous cell carcinomas were characterized by inhomogeneous staining for Cx26, -30 and -43. Regions of intensive expression alternated with regions of no expression. Cx32 could not be observed by immunofluorescence staining in laryngeal tissue.


CONCLUSIONS
In immunohistochemical terms, there was no alteration of the expression of Cx isoforms during carcinogenesis in the laryngeal epithelium. These results do not exclude a loss of functional intercellular gap junction communication by posttranslational modifications of Cx isoforms or disturbed Cx integration into the gap junction channel. Further studies should investigate potential defective gap junctional intercellular communication in cancer cells based on molecular studies.
Schneider
Berit
B
Department of Otorhinolaryngology/Clinical Department of Phoniatrics-Logopedics, General Hospital, University Hospital of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. Berit.Schneider@akh-wien.ac.at
Teschner
Magnus
M
Sudermann
Thomas
T
Pikula
Branko
B
Lautermann
Jürgen
J
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D000072259:Connexin 26; D017630:Connexins / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007820:Laryngeal Mucosa / Q000378:metabolism*; D007822:Laryngeal Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000378:metabolism*
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26