Department of Endocrinology, Beijing Ji Shui Tan Hospital, The 4th Medical College of Peking University, Beijing, P.R. China.
Int J Oncol. 2013 Jul;43(1):113-20. doi: 10.3892/ijo.2013.1913. Epub 2013 Apr 22.
Increasing evidence has shown that cancer stem cells or tumor initiating cells are the 'root cause' of malignant cancers. However, the exact origin of cancer stem cells still remains obscure in thyroid research. EMT has been implicated in the initiation and conversion of early-stage tumors into invasive malignancies and is associated with the stemness of cancer cells. Based on these facts, a new hypothesis was suggested that EMT induces cancer stem cell generation and tumor progression in human thyroid cancer cells in vitro. In the present study, FTC133 cells identified as EMT-negative cells were used for EMT induction by HIF‑1α transfection. Overexpression of HIF-1α induced FTC133 cells to undergo EMT, downregulated the epithelial markers E-cadherin, upregulated the mesenchymal marker vimentin, and associated with highly invasive and metastatic properties. Most importantly, the induction of EMT promoted the stem-like side population cell proportion in the FTC133 cells. These results indicate that EMT induction promotes CSC traits and cell proportions in the thyroid cancer cells, which implies that EMT could induce cancer stem cell generation and tumor progression in thyroid cancers. Further understanding of the role of EMT and cancer stem cells in cancer progression may reveal new targets for the prevention or therapy of thyroid cancers.
越来越多的证据表明，癌症干细胞或肿瘤起始细胞是恶性癌症的“根源”。然而，在甲状腺研究中，癌症干细胞的确切起源仍然不清楚。EMT 被认为参与了早期肿瘤的发生和向侵袭性恶性肿瘤的转化，并与癌细胞的干性有关。基于这些事实，提出了一个新的假设，即 EMT 在体外诱导人甲状腺癌细胞中癌症干细胞的产生和肿瘤进展。在本研究中，使用被鉴定为 EMT 阴性的 FTC133 细胞通过 HIF-1α 转染进行 EMT 诱导。HIF-1α 的过表达诱导 FTC133 细胞发生 EMT，下调上皮标志物 E-钙黏蛋白，上调间充质标志物波形蛋白，并与高度侵袭性和转移性特性相关。最重要的是，EMT 的诱导促进了 FTC133 细胞中类似干细胞的侧群细胞比例。这些结果表明，EMT 诱导促进了甲状腺癌细胞中 CSC 特征和细胞比例的增加，这意味着 EMT 可能在甲状腺癌中诱导癌症干细胞的产生和肿瘤进展。进一步了解 EMT 和癌症干细胞在癌症进展中的作用，可能为预防或治疗甲状腺癌揭示新的靶点。
