Subpopulations of cancer stem cells found in papillary thyroid carcinoma
Subpopulations of cancer stem cells found in papillary thyroid carcinoma
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DOI：
10.1016/j.yexcr.2017.12.017
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发表时间：
2018-01-15
影响因子：
3.7
通讯作者：
Yuan, Xiangpeng
中科院分区：
文献类型：
--
作者：
Mirshahidi, Saied;Simental, Alfred;Yuan, Xiangpeng
甲状腺乳头状癌（PTC）是最常见的甲状腺癌，虽然预后良好，但肿瘤复发仍然是一个主要的临床挑战。实验室细胞系和临床标本的研究表明，PTC可能遵循癌症干细胞（CSC）模型。然而，与PTC发生和进展相关的CSC特征在很大程度上仍然未知。在这里，我们研究了从临床PTC原代培养中分离的球形肿瘤细胞群。这些球形细胞由醛脱氢酶阳性（ALDH(+)）和醛脱氢酶阴性（ALDH(-)）细胞亚群组成，并表现出细胞分裂的分层模式。结合选择性消耗、特异性抑制和细胞分选，我们发现两个球细胞亚群都能够自我更新并独立启动异种移植物肿瘤，并满足CSC的定义。重要的是，当这些亚群一起起作用时，与单独的任何一个亚群相比，癌症启动效率和异种移植物肿瘤进展显著增强。这些数据揭示了ALDH(-) CSC在PTC生物学中的重要作用，并表明CSC亚群协同控制PTC的发生和进展。总之，我们的研究表明，从临床标本中分离出的CSC亚群为研究PTC发病机制和开发有效的治疗方法提供了前所未有的机会。
Papillary thyroid carcinoma (PTC) is the most common form of thyroid cancer and while it has a generally good prognosis, tumor recurrence remains a major clinical challenge. Studying laboratory cell lines as well as clinical specimens indicate that PTC may follow the cancer stem cell (CSC) model. However, CSC characteristics relevant in PTC initiation and progression remain largely unknown. Here we studied a population of sphere-growing tumor cells isolated from primary cultures of clinical PTC. These sphere-growing cells consisted of aldehyde dehydrogenase positive (ALDH(+)) and ALDH negative (ALDH(-)) cell subpopulations and demonstrated a hierarchical pattern of cell division. Using combinations of selective depletion, specific inhibition and cell sorting, we found that both subpopulations of the sphere cells were able to self-renew and initiate xenograft tumors independently, and fulfilled the definition of CSC. Importantly, when the subpopulations functioned together, the cancer-initiation efficiency and the xenograft tumor progression were significantly enhanced compared to either subpopulation alone. These data revealed crucial roles of ALDH(-) CSC in PTC biology and suggested that CSC subpopulations function cooperatively to control PTC initiation and progression. Together, our study indicates that CSC subpopulations isolated from clinical specimens offer unprecedented opportunities for investigating PTC pathogenesis and developing effective therapies.