Tumor and normal thyroid spheroids: from tissues to zebrafish.
BACKGROUND
Multicellular spheroids represent an interesting experimental model with promising applications in the pre-clinical studies on anticancer drugs. We recently demonstrated that thyroid spheroids recapitulate the features of the original tissues, in either the differentiated and "stem-like" components. Here we were aimed to characterize thyroid spheroids and to investigate in vivo the proangiogenic potential of patient-derived xenografts (PDX) of spheroids obtained from papillary thyroid cancer (PTC) and the matched normal tissues.


METHODS
Spheroids cultures were obtained from 11 PTCs and matched normal tissues and characterized by immunohistochemistry. The expression of p53, involved in the regulation of stem cell homeostasis, was evaluated. The proangiogenic effect of thyroid spheroids was assessed by the injection in zebrafish embryos.


RESULTS
Thyroid spheroids are enriched in stem-like cells, as shown by the positivity for the stem cell marker OCT4, and by the low level of p53 expression. Interestingly, PTCs and normal thyroid tissues have a detectable p53 expression, whereas the derived spheroids are mainly constituted by cells that express p53 at a lower level. Finally, we show that PDXs derived from PTC or normal spheroids stimulate the migration and the growth of sprouting vessels toward the implant into the zebrafish embryos.


CONCLUSIONS
We report the characterization of multicellular spheroids obtained from PTCs and normal thyroid tissues, showing that they are enriched in stem-like cells. Moreover, we established xenografts of spheroids in zebrafish, demonstrating that they stimulate neoangiogenesis. This in vivo model could be considered as a valuable platform to test the effects of anticancer drugs.
Division of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano, Milan, Italy - valentina.cirello@unimi.it.|Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy - valentina.cirello@unimi.it.
Valentina
V
Cirello
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
Germano
G
Gaudenzi
Division of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano, Milan, Italy.
Elisa S
ES
Grassi
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
Carla
C
Colombo
Endocrine Surgery Unit, Ca' Granda Foundation and Institute for Research and Care, Milan, Italy.
Leonardo
L
Vicentini
Division of Pathology, Ca' Granda Foundation and Institute for Research and Care, Milan, Italy.|Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
Stefano
S
Ferrero
Division of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano, Milan, Italy.|Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
Luca
L
Persani
Division of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano, Milan, Italy.|Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
Giovanni
G
Vitale
Division of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano, Milan, Italy.|Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
Laura
L
Fugazzola
D000818:Animals; D002291:Carcinoma, Papillary / Q000473:pathology* / Q000648:ultrastructure*; D006801:Humans; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology; D018874:Spheroids, Cellular / Q000473:pathology* / Q000648:ultrastructure*; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000473:pathology* / Q000648:ultrastructure*; D013964:Thyroid Neoplasms / Q000473:pathology* / Q000648:ultrastructure*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D015027:Zebrafish
D016159:Tumor Suppressor Protein p53