Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
Hum Pathol. 2013 Sep;44(9):1707-13. doi: 10.1016/j.humpath.2013.01.009. Epub 2013 Mar 22.
Cancer stem-like cells are a subpopulation of self-renewing stem cells in cancers that are more resistant to chemotherapy and radiation therapy. Evidence supporting the existence of cancer stem-like cells in thyroid and in many other solid tissue cancers is rapidly accumulating. These cells have been studied using specific biomarkers such as CD133, CD44, and aldehyde dehydrogenase enzymes. Putative cancer stem-like cells can be studied in vitro using serum-free media supplemented with basic fibroblast growth factor and epidermal growth factor grown in nonadherent culture (ultra-low attachment plates) or in extracellular matrix leading to cell spheres formation in vitro. Cancer stem-like cells can also be separated by fluorescent cell sorting and used for in vitro or in vivo studies. Injection of enriched populations of cancer stem-like cells (also referred to as tumor initiating cells) into immunodeficient mice often results in rapid growth of xenografts, which express cancer stem-like cell biomarkers. Human cancer stem-like cells have been identified in thyroid cancer cell lines including papillary, follicular, medullary, and anaplastic carcinoma cell lines. They have also been identified in primary thyroid cancers and have been shown to have similar properties as the cancer stem-like cells in thyroid cancer cell lines. Immunohistochemical staining with CD133 and other biomarkers has been used to characterize thyroid cancer stem-like cells in paraffin sections of thyroid cancers. Recent studies of epithelial-mesenchymal transition in which cells lose their epithelial features and acquire mesenchymal phenotypes have shown that these changes are present in thyroid cancers. Biomarkers used to characterize epithelial-mesenchymal transition have also been studied in primary thyroid cancers. A close relationship between epithelial-mesenchymal transition and stem cell features of cancers has been identified in recent studies. New discoveries in this field may lead to more effective therapies for highly aggressive and lethal thyroid cancers.
肿瘤干细胞样细胞是癌症中自我更新干细胞的一个亚群，对化疗和放疗更具抵抗力。越来越多的证据支持甲状腺和许多其他实体组织癌症中存在肿瘤干细胞样细胞。这些细胞已经使用特定的生物标志物如 CD133、CD44 和醛脱氢酶进行了研究。在无血清培养基中，通过添加碱性成纤维细胞生长因子和表皮生长因子，可以在非贴壁培养（超低附着平板）或细胞外基质中培养肿瘤干细胞样细胞，从而形成体外细胞球。也可以通过荧光细胞分选分离肿瘤干细胞样细胞，并用于体外或体内研究。将富含肿瘤干细胞样细胞（也称为起始肿瘤细胞）的细胞群注入免疫缺陷小鼠中，通常会导致异种移植物的快速生长，这些异种移植物表达肿瘤干细胞样细胞的生物标志物。在甲状腺癌细胞系中，包括乳头状、滤泡状、髓样和间变性癌细胞系，已经鉴定出人类肿瘤干细胞样细胞。在原发性甲状腺癌中也已经鉴定出它们，并显示出与甲状腺癌细胞系中的肿瘤干细胞样细胞相似的特性。用 CD133 和其他生物标志物进行免疫组织化学染色，已经用于对甲状腺癌石蜡切片中的肿瘤干细胞样细胞进行特征描述。最近对上皮-间充质转化的研究表明，细胞失去上皮特征并获得间充质表型，这些变化存在于甲状腺癌中。用于描述上皮-间充质转化的生物标志物也在原发性甲状腺癌中进行了研究。最近的研究表明，上皮-间充质转化与癌症的干细胞特征之间存在密切关系。这一领域的新发现可能会为高度侵袭性和致命性的甲状腺癌提供更有效的治疗方法。
