Connexin expression and gap junctional intercellular communication in human squamous cell carcinoma of the head and neck

OBJECTIVE: Our laboratory is investigating the role that gap junction intercellular channels (composed of proteins called connexins) play in communicating apoptotic signals from therapeutically targeted squamous cell carcinoma of the head and neck (SCCHN) cells to adjacent, untreated, "bystander" cells (bystander effect). The nature of this research underscores the importance of delineating connexin expression patterns in SCCHN, and how this correlates with gap junctional intercellular communication (GJIC) and bystander effects. STUDY DESIGN: The GJIC activity of a diverse panel of SCCHN cell lines, as well as normal oral epithelial (NOE) cell controls was determined in vitro. These data were correlated with connexin expression patterns determined through connexin 43 and connexin 26 immunofluorescence. RESULTS: Cell lines with retained GJIC activity all expressed connexin 43 on the cell membrane. Cell lines that did not communicate microinjected lucifer yellow (lost GJIC activity) showed no connexin expression, either at the cell membrane or in the cytosol. Connexin 26 was not expressed in any of our SCCHN cell lines, whereas both connexin 43 and connexin 26 were expressed in the NOE cell controls. Furthermore, connexin 43 introduction into a GJIC (and connexin) deficient SCCHN cell line conferred no growth inhibitory effect. CONCLUSION: Connexin 43 expression correlates with retained GJIC in SCCHN in vitro. Connexin 26 may have a role as a tumor suppressor in SCCHN. SIGNIFICANCE: The data presented have relevance to our ongoing investigations of gap-junction mediated bystander effects in SCCHN and are being expanded to investigations on actual SCCHN tumor specimens. (C) 2006 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved.