Expression of Gap Junction Proteins (Connexin 26, 30, 32, 43) in Normal Mucosa, Hyperkeratosis and Carcinoma of the Human Larynx

Abstract

Introduction: 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. Method: 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 caricnomas 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. Conclusion: 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.

Connexin 43 (Cx43) Expression in Laryngeal Squamous Cell Carcinomas: Preliminary Data on Its Possible Prognostic Role

“…Very few studies have been reported about Cx43 expression in head and neck squamous cell carcinomas, mainly in laryngeal squamous cell carcinoma [19][20][21] In our paper, high or moderate Cx43 expression has been detected in overall well differentiated squamous cell carcinomas (G1), while low or negative Cx43 expression has been found in poorly differentiated carcinomas (G3): as expected, these data confirmed the relationship between low and high grade carcinomas and Cx43 expression.…”

Specific localisation of gap junction protein connexin 32 in the gastric mucosa of horses

“…A lack of Cx32 in stratified squamous epithelium has also been described in the laryngeal tissue by Schneider et al (2002). Further studies are necessary to find out if the lack of Cx32 in the horse gastric squamous mucosa contributes to its high susceptibility to develop peptic ulcers.…”

Human Embryonic Stem Cell-Derived Epithelial Cells in a Novel In Vitro Model of Vocal Mucosa

“…10 Adherens junctions and desmosomes were also observed consistent with their presence in humans. [10][11][12] However, despite the presence of intercellular …”

“…Therefore, in addition to demonstrating an epithelial phenotype, candidate tissue constructs must also demonstrate the presence of important components of the epithelial barrier, including intercellular junctions. The native vocal fold epithelium contains intercellular junctions, including tight junctions, 10,11 gap junctions, 12 adherens junctions, 11 and desmosomes. 10 While Long and colleagues 9 reported the presence of e-cadherin, a marker of adherens junctions, in their model, further evidence of intercellular junctions was not provided.…”