JOURNAL ARTICLE

In vitro identification and characterization of CD133(pos) cancer stem-like cells in anaplastic thyroid carcinoma cell lines

Giovanni Zito, Pierina Richiusa, Alessandra Bommarito, Elvira Carissimi, Leonardo Russo, Antonina Coppola, Monica Zerilli, Vito Rodolico, Angela Criscimanna, Marco Amato, Giuseppe Pizzolanti, Aldo Galluzzo, Carla Giordano
PloS One 2008, 3 (10): e3544
18958156

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 CD133(pos) 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/CD133(pos) cells exhibited higher proliferation, self-renewal, colony-forming ability in comparison with ARO/CD133(neg). Furthermore, ARO/CD133(pos) showed levels of thyroid transcription factor TTF-1 similar to the fetal thyroid cell line TAD-2, while the expression in ARO/CD133(neg) was negligible. The expression of the stem cell marker OCT-4 detected by RT-PCR and flow cytometry was markedly higher in ARO/CD133(pos) in comparison to ARO/CD133(neg) 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/CD133(pos) when compared with ARO/CD133(neg) cells.

CONCLUSIONS/SIGNIFICANCE: We describe CD133(pos) cells in ATC cell lines. ARO/CD133(pos) 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.

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