Changes in the expression of the potassium channels TASK1, TASK3 and TRESK in a rat model of oral squamous cell carcinoma and their relation to malignancy.

OBJECTIVES: Potassium channels have been proposed to promote cancer cell proliferation and metastases. Thus, we investigated the expression pattern of three 2-pore domain potassium channels (K2Ps) TASK1, TASK3 and TRESK in advanced oral squamous cell carcinoma (OSCC), the commonest oral malignancy. DESIGN: We used 4-nitroquinoline-1-oxide (4-NQO) to induce high grade OSCC in male adult rats. We then used immunohistochemistry and Western blotting to study the distribution and expression pattern of TASK1, TASK3 and TRESK in normal versus cancerous tissue. We also examined the expression of ß-tubulin III (ß-tub3), a marker associated with resistance to taxane-based chemotherapy and poor patient prognosis, and its correlation with the K2Ps. Finally, we studied the expression of TASK1, TASK3 and TRESK in human samples of SCC of oral origin. RESULTS: We found that TASK3 was significantly up-regulated whereas TASK1 and TRESK were both significantly down-regulated in advanced, poorly differentiated OSCC. Both, rat and human SCC showed a significant increase in the expression of ß-tub3. Interestingly, the expression of the latter correlated positively and significantly with TASK3 and TRESK but not TASK1 in rat OSCC. Our initial results showed a similar pattern of up and down regulation and correlation with ß-tub3 for these three K2Ps in human SCC. CONCLUSIONS: The changes in expression and the co-localization with a marker of resistance to taxanes like ß-tub3 turn TASK1, TASK3 and TRESK into potentially new prognostic tools and possibly new therapeutic targets for OSCC.

Variation in Langerhans cell number and morphology between the upper and lower regions of the human esophageal epithelium.

Langerhans cells (LCs) are dendritic components of stratified epithelia, presenting antigens to other cells of the immune system that play a crucial role in local defense. The paucity of information about their significance in the esophageal mucosa was addressed by studying their distribution and morphology in this particular location. LCs were identified by immunohistochemical detection of CD1a, a cell-specific marker, using a monoclonal antibody, as well as by electron microscopic identification of characteristic Birbeck granules, among other typical morphological features. Cell counts carried out at 25 and 35 cm distal to the dental arch demonstrated significant differences in number and size between the two locations. The upper region contained 10.4 +/- 0.8 cells (mean +/- SEM) vs. 18.4 +/- 1.4 cells in the lower region. Also, cells in the lower region were larger and appeared to have longer dendritic processes. To our knowledge this is the first report of regional differences in number and morphology of LCs in human esophageal mucosa.