Abstract 4074: Cancer stem cells in tobacco-induced carcinogenesis and subsequent effect of ATRA-based chemoprevention

Introduction Chemoprevention is potentially the most effective method to lower the prevalence of head and neck squamous cell carcinomas (HNSCC), the sixth most common type of malignancy worldwide. The chemopreventive effects of retinoids against HNSCC have been previously reported. Retinoids however; relapse following cessation of medication is a critical problem that prevents its clinical use. The objective of this study was to determine the possible mechanism of retinoid resistance by exploring cancer stem cell mediated pathways. Experimental Procedures. In vitro cell line models of normal (NOK) and dysplastic oral keratinocytes (DOK) are being exposed to tobacco to assess the process of carcinogenic progression. The progression in the DOK and HOK cell lines will be assessed by proliferation, migration and invasion assays. The expression of stem cell markers/pathways (CD44/Hyaluronan, Wnt, Notch1, ALDH1A1) during the process of progression will be evaluated using QPCR and FACS. These cell lines will then be treated with ATRA and the subsequent effects on transformation and CSC-specific pathways further evaluated. Summary To this end, immunostaining of normal oral mucosa, potentially malignant lesions (n = 93) and malignant lesions (n = 48) for the stem cell marker CD44 was performed. CD44+ cells were found at a density of 58.57/hpf in normal mucosa, 61.56/hpf in mild dysplasia, 119.44/hpf in moderate dysplasia, and 107.6/hpf in severe dysplasia. The density of CD44+ cells in WDSCC, MDSCC and PDSCC were 183.4, 105 and 160/hpf respectively, indicates CSC cells may represent a marker of malignant progression The cell lines are currently under exposure to tobacco and the transformational changes being documented. Apart from the studies on the changes specific to CSCs, high throughput secretome and proteomic studies are also being planned to evaluate the global changes effected due to tobacco as well as due to subsequent treatment with ATRA. Conclusion This study hence attempts to provide novel insight into tobacco-induced carcinogenesis and mechanism of resistance to retinoid-based chemoprevention. Note: This abstract was not presented at the meeting. Citation Format: Subin Surendran, Christina Mimikos, Amritha Suresh, Wesley L. Hicks, Mukund Seshadri, Moni A. Kuriakose. Cancer stem cells in tobacco-induced carcinogenesis and subsequent effect of ATRA-based chemoprevention. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4074. doi:10.1158/1538-7445.AM2015-4074