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.


METHODS
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.


CONCLUSIONS
Connexin 43 expression correlates with retained GJIC in SCCHN in vitro. Connexin 26 may have a role as a tumor suppressor in SCCHN.


CONCLUSIONS
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.
Frank
Douglas K
DK
Department of Otolaryngology-Head and Neck Surgery and the Head and Neck Cancer Molecular Biology Research Laboratory, Division of Basic Sciences, New York, New York, USA. dfrank@bethisraelny.org
Szymkowiak
Bozena
B
Hughes
Cynthia A
CA
D017209:Apoptosis / Q000502:physiology; D024201:Bystander Effect / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000503:physiopathology*; D002450:Cell Communication / Q000502:physiology*; D002452:Cell Count; D000072259:Connexin 26; D018031:Connexin 43 / Q000032:analysis*; D017630:Connexins / Q000032:analysis*; D004847:Epithelial Cells / Q000502:physiology; D005455:Fluorescent Antibody Technique; D017629:Gap Junctions / Q000502:physiology*; D006258:Head and Neck Neoplasms / Q000503:physiopathology*; D006801:Humans; D009061:Mouth Mucosa / Q000166:cytology; D014407:Tumor Cells, Cultured
D018031:Connexin 43; D017630:Connexins; D000072259:Connexin 26