Abstract 232: Cancer stem cells and cisplatin.

Abstract

Abstract Introduction: Cisplatin is an important chemotherapeutic agent, which has resulted in higher overall response rates when combined with 5-FU or taxane combinations in treating squamous cellular carcinoma of the head and neck. However, HNSCC tumor response rates to cisplatin range from 20-30%, a major clinical hurdle today. To address this issue thoroughly, we investigated the resistance to cisplatin in HNSCC under the purview of the cancer stem cell hypothesis, using the widely studied CSC marker combinations of, CD44+ 24- and ALDH-Hi. In order to get a broader perspective on this issue, we worked on multiple HNSCC tumor cell lines with varying degrees of cisplatin resistance, arising from tumors of the pharynx, larynx, tongue, tonsils, alveolus, hypopharynx and supraglottis. Methods: Seven HNSCC cell lines were analyzed for their CSC percentage through FACS, utilizing CD44+ 24- and ALDH-Hi marker systems. Cisplatin IC-50 for each of these seven cell lines was then determined by plotting percent viability vs. drug concentration curves. The remaining viable cells after cisplatin treatment were then analyzed through FACS for their CD44+ 24- and ALDH-Hi percentages in order to compare with the CSC percentage in the untreated HNSCC lines. Results: There was a wide variation in the percentages of CD44+24- and ALDH-Hi cells across these seven HNSCC lines. An inverse correlation between the initial percentages of CD44+24- and ALDH-Hi cells and the corresponding cisplatin IC-50 values was seen. HNSCC cell lines that had lower IC-50 values for cisplatin displayed greater cell viability at higher concentrations of cisplatin. This was evident by a long tail in the sigmoidal dose response curve. The number of viable cells at the end of cisplatin treatment had a linear relationship with the overall percentage of CSCs in the control untreated cell lines. Conclusion: Our results suggest that the resistance offered by the CD44+24- and ALDH1-Hi cells is apparent only once the initial 50% loss of cells occurs. This in vitro biphasic decline in percent viable cells clearly indicates that HNSCC cisplatin resistance is a twofold problem. The bulk of non-cancer stem cells within a tumor can acquire resistance to cisplatin via multiple molecular pathways, but this is only a front line cover of resistance to the resistance offered by the cancer stem cells. Citation Format: Vishnu Modur. Cancer stem cells and cisplatin. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 232. doi:10.1158/1538-7445.AM2013-232