Tumor and normal thyroid spheroids: from tissues to zebrafish

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Abstract

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.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalMinerva Endocrinologica
Volume43
Issue number1
DOIs
Publication statusPublished - Mar 2018

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Zebrafish
Thyroid Gland
Factor IX
Stem Cells
Cellular Spheroids
Neoplasms
Heterografts
Embryonic Structures
Pharmaceutical Preparations
Homeostasis
Theoretical Models
Immunohistochemistry
Injections
Growth

Keywords

  • Animals
  • Carcinoma, Papillary/pathology
  • Humans
  • Neoplasm Transplantation
  • Neovascularization, Pathologic/pathology
  • Spheroids, Cellular/pathology
  • Thyroid Cancer, Papillary
  • Thyroid Gland/pathology
  • Thyroid Neoplasms/pathology
  • Tumor Suppressor Protein p53/genetics
  • Zebrafish

Cite this

@article{38850feadc7542faad58d41db3a0ec71,
title = "Tumor and normal thyroid spheroids: from tissues to zebrafish",
abstract = "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.",
keywords = "Animals, Carcinoma, Papillary/pathology, Humans, Neoplasm Transplantation, Neovascularization, Pathologic/pathology, Spheroids, Cellular/pathology, Thyroid Cancer, Papillary, Thyroid Gland/pathology, Thyroid Neoplasms/pathology, Tumor Suppressor Protein p53/genetics, Zebrafish",
author = "Valentina Cirello and Germano Gaudenzi and Grassi, {Elisa S} and Carla Colombo and Leonardo Vicentini and Stefano Ferrero and Luca Persani and Giovanni Vitale and Laura Fugazzola",
year = "2018",
month = "3",
doi = "10.23736/S0391-1977.17.02610-4",
language = "English",
volume = "43",
pages = "1--10",
journal = "Minerva Endocrinologica",
issn = "0391-1977",
publisher = "Edizioni Minerva Medica S.p.A.",
number = "1",

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TY - JOUR

T1 - Tumor and normal thyroid spheroids

T2 - from tissues to zebrafish

AU - Cirello, Valentina

AU - Gaudenzi, Germano

AU - Grassi, Elisa S

AU - Colombo, Carla

AU - Vicentini, Leonardo

AU - Ferrero, Stefano

AU - Persani, Luca

AU - Vitale, Giovanni

AU - Fugazzola, Laura

PY - 2018/3

Y1 - 2018/3

N2 - 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.

AB - 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.

KW - Animals

KW - Carcinoma, Papillary/pathology

KW - Humans

KW - Neoplasm Transplantation

KW - Neovascularization, Pathologic/pathology

KW - Spheroids, Cellular/pathology

KW - Thyroid Cancer, Papillary

KW - Thyroid Gland/pathology

KW - Thyroid Neoplasms/pathology

KW - Tumor Suppressor Protein p53/genetics

KW - Zebrafish

U2 - 10.23736/S0391-1977.17.02610-4

DO - 10.23736/S0391-1977.17.02610-4

M3 - Article

C2 - 28146140

VL - 43

SP - 1

EP - 10

JO - Minerva Endocrinologica

JF - Minerva Endocrinologica

SN - 0391-1977

IS - 1

ER -