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 language | English |
|---|---|
| Pages (from-to) | 1-10 |
| Number of pages | 10 |
| Journal | Minerva Endocrinologica |
| Volume | 43 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Mar 2018 |
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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
Tumor and normal thyroid spheroids : from tissues to zebrafish. / Cirello, Valentina; Gaudenzi, Germano; Grassi, Elisa S; Colombo, Carla; Vicentini, Leonardo; Ferrero, Stefano; Persani, Luca; Vitale, Giovanni; Fugazzola, Laura.
In: Minerva Endocrinologica, Vol. 43, No. 1, 03.2018, p. 1-10.Research output: Contribution to journal › Article
}
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 -