Abstract 60: Characterization of papillary thyroid carcinoma primary cell culture derived cancer stem-like cells

Papillary thyroid carcinoma is the most frequent type of thyroid cancer. Although most PTC patients can be treated successfully and have an excellent prognosis, 10-20% of patients with stage I/II disease experience recurrence, developing invasive tumors and/or distant metastases. For these patients, a greater understanding of the mechanisms that govern PTC tumor initiation and progression would aid in developing effective therapeutic strategies to target the disease. It is becoming evident that thyroid tumors may follow the cancer stem cell model (CSC), where a population of cancer stem cells is responsible for tumor initiation and progression. Currently, the CSC biology of PTC is still poorly understood. In this study, we isolated sphere-growing cells from PTC specimen-derived primary cells using serum-free culture. In vivo transplantation analysis revealed that the sphere cells were capable of generating xenograft tumors that recapitulated the original tumor phenotypes. Analyzing the sphere cells for aldehyde dehydrogenase (ALDH) expression, a marker commonly used in CSC study, revealed that around half of the sphere cells did not express ALDH. When the sphere cells were sorted into ALDH - and ALDH + subpopulations, both subpopulations demonstrated capabilities of re-initiating subspheres in vitro and generating serial xenograft tumors in vivo with the ALDH + cells exhibiting a slightly higher efficiency of sphere-formation and cancer-initiation. Of major importance, the sphere cell population without sorting demonstrated the higher levels of cancer-initiating cell frequency, and quicker xenograft tumor progression than the subpopulations of ALDH - and ALDH + cells. Furthermore, histologic investigation of xenograft tumors generated by the sphere population and the sphere-sorted subpopulations, respectively, revealed similar morphological features that recapitulated the characteristics of original human PTC from which the sphere cells were isolated. Our data established a vital role of ALDH - cancer stem-like cells and revealed a potential synergistic activity between ALDH - and ALDH + cells in the tumor initiation and progression of PTC. Further exploring the biological property of ALDH - cancer stem-like cells may lead to development of novel therapeutic solutions to treating aggressive PTC. Citation Format: Alfred Simental, Steve Lee, Pedro A. De Andrade Filho, Nathaniel R. Peterson, Saied Mirshahidi, Penelope Duerksen-Hughes, Xiangpeng Yuan. Characterization of papillary thyroid carcinoma primary cell culture derived cancer stem-like cells [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 60.