PloS One：发现一种新的癌症干细胞

　　

生物通报道，来自意大利巴勒莫大学分子内分泌学系实验室、人体病理学实验室从甲状腺癌细胞系中分离到癌症干细胞样细胞，该细胞高度表达CD33。相关的成果发布在10月29日的PloS One上。

 

近年来，科学家们认为癌症的发生其实只与一部分的细胞类型有关，就是这小部分的异常细胞导致癌症的发生，科学家们将这些细胞称为：癌症干细胞（cancer stem cells，CSCs）。、

甲状腺未分化癌（Anaplastic Thyroid Carcinoma，ATC）：是人类恶性肿瘤中恶性程度最高的一类，致死率极高，不论治疗与否，平均病程6个月。在甲状腺未分化癌组织里存在有癌症干细胞样细胞，CD33是被认为是正常或是癌性细胞表面的活性标记，尽管CD33的具体生物学意义暂时不清，但是CD33是干细胞表面的标记已经得到一致认定。

 

研究者在体外对高度表达CD33甲状腺癌细胞系进行分析。结果发现ARO/CD33阳性的细胞表现出干细胞样的特征。ARO是癌性的标记。ARO/CD33阳性的细胞繁殖能力强，具有自我更新的能力，表达OCT-4，对化学治疗作用具有高度的耐受性。同时，对这些干细胞样细胞进行分析发现，它们还表达甲状腺特征性的标记TTF-1和onfFN。

 

将这些结果整合在一起，研究者推测，这一类细胞也许就是甲状腺未分化癌的癌症干细胞。如果推测属实，该理论成果可能为甲状腺未分化癌的诊断、治疗带来新的契机。

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原文摘要：In Vitro Identification and Characterization of CD133pos Cancer Stem-Like Cells in Anaplastic Thyroid Carcinoma Cell Lines

 

【Abstract】

Background

Recent publications suggest that neoplastic initiation and growth are dependent on a small subset of cells, termed cancer stem cells (CSCs). Anaplastic Thyroid Carcinoma (ATC) is a very aggressive solid tumor with poor prognosis, characterized by high dedifferentiation. The existence of CSCs might account for the heterogeneity of ATC lesions. CD133 has been identified as a stem cell marker for normal and cancerous tissues, although its biological function remains unknown.

 

Methodology/Principal Findings

ATC cell lines ARO, KAT-4, KAT-18 and FRO were analyzed for CD133 expression. Flow cytometry showed CD133pos cells only in ARO and KAT-4 (64±9% and 57±12%, respectively). These data were confirmed by qRT-PCR and immunocytochemistry. ARO and KAT-4 were also positive for fetal marker oncofetal fibronectin and negative for thyrocyte-specific differentiating markers thyroglobulin, thyroperoxidase and sodium/iodide symporter. Sorted ARO/CD133pos cells exhibited higher proliferation, self-renewal, colony-forming ability in comparison with ARO/CD133neg. Furthermore, ARO/CD133pos showed levels of thyroid transcription factor TTF-1 similar to the fetal thyroid cell line TAD-2, while the expression in ARO/CD133neg was negligible. The expression of the stem cell marker OCT-4 detected by RT-PCR and flow cytometry was markedly higher in ARO/CD133pos in comparison to ARO/CD133neg cells. The stem cell markers c-KIT and THY-1 were negative. Sensitivity to chemotherapy agents was investigated, showing remarkable resistance to chemotherapy-induced apoptosis in ARO/CD133pos when compared with ARO/CD133neg cells.

 

Conclusions/Significance

We describe CD133pos cells in ATC cell lines. ARO/CD133pos cells exhibit stem cell-like features - such as high proliferation, self-renewal ability, expression of OCT-4 - and are characterized by higher resistance to chemotherapy. The simultaneous positivity for thyroid specific factor TTF-1 and onfFN suggest they might represent putative thyroid cancer stem-like cells. Our in vitro findings might provide new insights for novel therapeutic approaches.