Retinoic Acid Promotes Iodine Uptake Via Up-regulating NIS in Medullary Thyroid Cancer Stem Cells

MTC accounts around 5%-10% of thyroid cancer, and the death rate is more than 10%. It has a poor capability of iodine uptake which limits the way of therapy. Furthermore, many people believe that MTCSCs may play significant roles in metastasis and recurrence of MTC. Cancer stem cells (CSCs) have been reported in several solid tumors and in cancer cell lines (Reya et al., 2001; Reya et al., 2001; Ailles and Weissman, 2007; Lobo et al., 2007). Recently, people believed that only a few cells of CSCs have the capacity to sustain the growth of tumor. And this subpopulation of cells are capable of self-renew, proliferate and differentiate into other tumor cells (Jiang et al., 2012; Tabarestani and Ghafouri-Fard, 2012; Francipane et al., 2013). It also expresses high levels of ABCG2 and OCT4, which may cause their resistance to the conventional therapies of cancer (Tabarestani and Ghafouri-Fard, 2012; Zhang et al., 2012). Thus, if we find a way to eliminate the CSCs, we may cure the cancer. All-trans-retinoic acid (ATRA) has the capacity of inducing differentiation, inhibiting proliferation and promoting apoptosis of many tumors and CSCs. It can induce differentiation of acute promyelocytic leukemia stem cells, and increase 5-year survival rate with arsenic trioxide (Cunha De Santis et al., 2007; Tomita et al., 2013). The sodium iodide symporter (NIS), as the first step in thyroid hormone biosynthesis, mediated thyroidal Itransport from the bloodstream to the colloid (Schmutzler et al., 1997; Foujilas et al., 2009; Damle et al., 2011). This