3). To date, our model is the first model to display the use of ASCs to produce metastatic thyroid cancer[28]. Zhu et al[29] demonstrated Ganetespib STA-9090 the existence of CSCs in MTC cell lines. These cells showed positivity for CD133 and displayed that RET proto-oncogene with basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) favor self-renewal in MTC cells. Additionally, these cells also expressed neuron specific markers namely β-tubulin isotype III and glial fibrillar acidic protein[29]. The purpose of demonstration of stemness markers using different cell

lines in the models suggests that these markers should be targeted with anintent to develop new efficacious treatment for refractory tumors. Figure 1 Histological images showing subcutaneous thyroid cancer mouse model. A: Hematoxylin and eosin stained microphotograph of tumor xenografts engrafted human thyroid cancer cell line (K1) with adipose-derived stem cells (ASCs) (× 100); B: HE microphotograph … Figure 2 Representative tumor from severe combined immunodeficiency mice injected with: (A) K1 + ASCs and (B) K1 alone. ASCs: Adipose-derived stem cells. Figure 3

Adipose-derived stem cells promote tumor growth of papillary thyroid cancer cells. K1 cells alone and K1 cells with ASCs (5 x 105 cells each) were injected subcutaneously into nude mice (n = 5, each group)[28]. ASC: Adipose-derived stem cell. FUTURE PERSPECTIVES Various genetic alterations defining oncogenic pathways in aggressive thyroid cancer have been recognized, yet, the ability to decode these mutations into novel anti-cancer therapies is limited. This recent discovery of thyroid CSCs marks an imperative stage for innovation

of efficient anti-cancer treatment for resistant tumors. It is a well-known fact that conventional anti-cancer therapies target differentiating/differentiated cells, which form the bulk of the tumor but are unable to generate new cells. If CSCs remain in the quiescent stage (dormant cells), they resist the therapy targeted for dividing cells. CSCs self-renewal and ability to constitute a very small proportion of the tumor, they might develop resistance to chemo- and Drug_discovery radiotherapy, ultimately causing the disease to relapse. It is possible that these cells may repair DNA damage more rapidly than normal cells[30]. A newer concept has been postulated by various authors that points out the metastatic potential of CSCs secondary to epithelial-mesenchymal transition (EMT) and the inverse [mesenchymal-epithelial transition (MET)] at an advanced stage of the disease[6,10,31,32]. A strong association between EMT/MET and CSCs has been highlighted recently, suggesting that EMT increases epithelial plasticity, confers tumor progression and therapeutic resistance to cancer cells. These transformed cells, then, behave like stem-cells similar to those seen in normal thyroid tissue.