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Endocrine Abstracts (2012) 29 P1782

ICEECE2012 Poster Presentations Thyroid cancer (108 abstracts)

Functional and molecular characterization of cancer stem cells in anaplastic thyroid carcinoma

V. Carina , G. Zito , G. Pizzolanti , P. Richiusa , L. Tomasello , M. Pitrone , C. Baiamonte , V. Guarnotta & C. Giordano


Faculty of Medicine, University, Palermo, Italy.


Anaplastic Thyroid Carcinoma (ATC) is the most aggressive thyroid gland malignancy characterized by undifferentiated morphology. It has been suggested that cancer stem cells (CSCs) might play a central role in ATC. Previously on the basis of CD133 positivity, our group suggested that CD133+ cancer stem cells (CSCs) might play a central role in ATC. Here we analyzed a panel of different stem cell markers in order to identify a peculiar CSC pattern in ATC.

Aim: i) to characterize CSCs from ex vivo ATC specimens; ii) to evaluate in a well characterized ATC cell line (SW1736) the percentage of CSCs and the influence of transcription factor SOX2 on Oct-4 and Nanog expression and drug resistance.

Methods: Ex vivo: Eight formalin-fixed, paraffin-embedded ATC specimens were analyzed by RT and qRT-PCR, immunohistochemistry and immunofluorescence for pluripotent CSC markers (CD133, SSEA4, Thy1, ABCG2, c-kit, SOX2, Oct-4, Nanog, Lin28, Klf4 and c-Myc). In vitro: CSC marker expression was evaluated in SW1736 cells by qRT-PCR, flow cytometry and immunofluorescence; the SOX2 effect on Oct-4 Nanog and ABCG2 expression and chemosensitivity were evaluated after SOX2 silencing by siRNA method.

Results: Stem cell markers expression in ATCs and SW1736 cell line proved to be as follows in the table.

SOX2 plays a pivotal role in this model: SOX2 silencing down-regulated Oct-4 (67.6%±2.0 P<0.05) and Nanog (85.5%±5.4 P<0.01) expression. SOX2 silencing sensitized SW1736 cells causing a significant mortality increase of 1.8 fold with 10 μM cisplatin and 1.4 (P<0.01) fold with 1.5 μM doxorubicin in comparison to control cells. Conclusions: The analysis of multiple pluripotent stem cell markers is useful to identify CSCs in ATC. In particular, SOX2 exerts a fundamental role in regulating Oct-4 and Nanog expression. Our data suggest that SOX2 switch-off may be essential for overcoming CSC chemotherapy resistance in ATC.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Table 1 Stem Cell Markers
CD133 SSEA4Thy1ABCG2c-kitSOX2Oct-4NanogLin28Klf4c-Myc
Control
ATCs +(4 out of 8) +(4 out of 8) + + + + + + +
SW1736 + + + + +

Volume 29

15th International & 14th European Congress of Endocrinology

European Society of Endocrinology 

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