Tumorigenic and Metastatic Activity of Human Thyroid Cancer Stem Cells
Tumorigenic and Metastatic Activity of Human Thyroid Cancer Stem Cells
复制标题
DOI：
10.1158/0008-5472.can-10-1994
复制
发表时间：
2010-11-01
期刊：
影响因子：
11.2
通讯作者：
Stassi, Giorgio
中科院分区：
文献类型：
--
作者：
Todaro, Matilde;Iovino, Flora;Stassi, Giorgio
甲状腺癌是最常见的内分泌恶性肿瘤，也是内分泌肿瘤中最常见的死亡原因。我们发现，甲状腺癌的致瘤能力局限于一小部分具有高乙醛脱氢酶(ALDH)活性和无限复制潜力的干细胞亚群。ALDH(HIGH)细胞可以作为肿瘤球体在体外无限扩增，在免疫低下的小鼠体内保留了致瘤潜能。原位注射微量的甲状腺癌干细胞重现了亲本肿瘤的行为，包括未分化甲状腺癌的侵袭性转移特征，这些特征是由甲状腺癌干细胞中cMET和Akt的结构性激活维持的。致瘤和转移性甲状腺癌细胞的鉴定可能为新靶向治疗的开发和临床前验证提供前所未有的临床前工具。癌症资源；70(21)；8874-85。(C)2010年AACR。
Thyroid carcinoma is the most common endocrine malignancy and the first cause of death among endocrine cancers. We show that the tumorigenic capacity in thyroid cancer is confined in a small subpopulation of stem-like cells with high aldehyde dehydrogenase (ALDH(high)) activity and unlimited replication potential. ALDH(high) cells can be expanded indefinitely in vitro as tumor spheres, which retain the tumorigenic potential upon delivery in immunocompromised mice. Orthotopic injection of minute numbers of thyroid cancer stem cells recapitulates the behavior of the parental tumor, including the aggressive metastatic features of undifferentiated thyroid carcinomas, which are sustained by constitutive activation of cMet and Akt in thyroid cancer stem cells. The identification of tumorigenic and metastagenic thyroid cancer cells may provide unprecedented preclinical tools for development and preclinical validation of novel targeted therapies. Cancer Res; 70(21); 8874-85. (C) 2010 AACR.