title: Resistance of papillary thyroid cancer stem cells to chemotherapy.
abstract: Thyroid carcinoma is the most common endocrine neoplasm, with the highest mortality rate of all the endocrine cancers. Among the endocrine malignancies, ~80% are papillary thyroid carcinomas (PTCs). In the initiation and progression of this tumor, genetic alterations in the mitogen-associated protein kinase pathway, including RAS point mutations, RET/PTC oncogene rearrangements and BRAF point mutations, play an important role, particularly in deciding targeted therapy. In the present study, a small population of thyroid tumor cells, known as tumor spheres, were isolated and characterized from PTC surgical samples. These spheres can be expanded indefinitelyin vitroand give rise to differentiated adherent cells when cultivated in differentiative conditions. The present study showed by reverse transcription-polymerase chain reaction and flow cytometric analysis that the undifferentiated PTC cells exhibited a characteristic antigen expression profile of adult progenitor/stem cells. The cells were more resistant to chemotherapeutics, including bortezomib, taxol, cisplatin, etoposide, doxorubicin and vincristine, than differentiated PTC cells and the majority possessed a quiescent status, as revealed by the various cell cycle characteristics and anti-apoptotic protein expression. Such advances in cancer thyroid stem cell biology may provide relevant information for future targeted therapies.
authors.affiliation: Cell Biology Unit, IOM Ricerca Srl, Viagrande, I-95029 Catania, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Giuffrida
authors.affiliation: Cell Biology Unit, IOM Ricerca Srl, Viagrande, I-95029 Catania, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Adamo
authors.affiliation: Cell Biology Unit, IOM Ricerca Srl, Viagrande, I-95029 Catania, Italy; Regenerative Medicine and Biomedical Technologies Unit, Department of Laboratory Medicine and Advanced Biotechnologies, Mediterranean Institute for Transplantation and Advanced Specialized Therapies, I-90127 Palermo, Italy.
authors.forename: Gioacchin
authors.initials: G
authors.lastname: Iannolo
authors.affiliation: Cell Biology Unit, IOM Ricerca Srl, Viagrande, I-95029 Catania, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Vicari
authors.affiliation: Department of Experimental Oncology, Mediterranean Institute of Oncology, Viagrande, I-95029 Catania, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Giuffrida
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, National Institute of Health, I-00161 Rome, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Eramo
authors.affiliation: Cell Biology Unit, IOM Ricerca Srl, Viagrande, I-95029 Catania, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Gulisano
authors.affiliation: Cell Biology Unit, IOM Ricerca Srl, Viagrande, I-95029 Catania, Italy; Department of Experimental Oncology, Mediterranean Institute of Oncology, Viagrande, I-95029 Catania, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Memeo
authors.affiliation: Department of Experimental Oncology, Mediterranean Institute of Oncology, Viagrande, I-95029 Catania, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Conticello
keywords: cancer stem cells; chemoresistance; differentiation; papillary thyroid carcinoma; tumor spheres