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.

Cytokine-induced killer cells co-cultured with complete tumor antigen-loaded dendritic cells, have enhanced selective cytotoxicity on carboplatin-resistant retinoblastoma cells.

Retinoblastoma (RB) is a challenging disease that affects mostly young children. Chemical therapy has been shown to have limitations during clinical practice, principally because of the ability of RB to become resistant to the treatment. Nevertheless, chemotherapy is still the main treatment for RB, and immunotherapy has become a promising treatment for most solid tumors with fewer side effects than traditional therapies. In this study, we explored the antitumor effects of cytokine-induced killer (CIK) cells co-cultured with dendritic cells (DCs) pulsed with complete tumor antigens (DC-Ag). Cytotoxicity and specificity were evaluated on an RB cell line (RB-Y79), on a human normal retina cell line (hTERT-RPE1) and a carboplatin-resistant RB cell line. Our results showed that CIK differentiation and cytotoxicity were enhanced by co-culturing CIKs with DC-Ag. Moreover, the co-culture improved the CIK proliferation rate by increasing IL-6 and decreasing IL-10 levels in the culture medium. Furthermore, the use of DC-Ag-CIK cells had little effect on normal retinal cells but high cytotoxicity on RB cells even on carboplatin-resistant retinoblastoma cells. This is the first study showing that DC cells pulsed with the complete tumor antigen improve proliferation, differentiation and cytotoxic activity of CIKs specific not only for RB but also for the chemotherapy-resistant form of the malady. Thus highly efficient immunotherapy based on DC-Ag-CIK cells may be a potential effective and safe mean of treating RB especially to patients where traditional chemical therapy has failed.