A novel orthotopic mouse model of human anaplastic thyroid carcinoma.
BACKGROUND
Orthotopic mouse models of human cancer represent an important in vivo tool for drug testing and validation. Most of the human thyroid carcinoma cell lines used in orthotopic or subcutaneous models are likely of melanoma and colon cancer. Here, we report and characterize a novel orthotopic model of human thyroid carcinoma using a unique thyroid cancer cell line.


METHODS
We used the cell line 8505c, originated from a thyroid tumor histologically characterized by anaplastic carcinoma cell features. We injected 8505c cells engineered using a green fluorescent protein-positive lentiviral vector orthotopically into the thyroid of severe combined immunodeficient mice.


RESULTS
Orthotopic implantation with the 8505c cells produced thyroid tumors after 5 weeks, showing large neck masses, with histopathologic features of a high-grade neoplasm (anaplasia, necrosis, high mitotic and proliferative indexes, p53 positivity, extrathyroidal invasion, lymph node and distant metastases) and immunoprofile of follicular thyroid cell origin with positivity for thyroid transcription factor-1 and PAX8, and for cytokeratins.


CONCLUSIONS
Here we describe a novel orthotopic thyroid carcinoma model using 8505c cells. This model can prove to be a reliable and useful tool to investigate in vivo biological mechanisms determining thyroid cancer aggressiveness, and to test novel therapeutics for the treatment of refractory or advanced thyroid cancers.
Nucera
Carmelo
C
Thyroid Cancer Research Laboratory, Unit of Endocrine Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nehs
Matthew A
MA
Mekel
Michal
M
Zhang
Xuefeng
X
Hodin
Richard
R
Lawler
Jack
J
Nose
Vânia
V
Parangi
Sareh
S
D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D009368:Neoplasm Transplantation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D013961:Thyroid Gland / Q000166:cytology / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*; D014162:Transfection
D048493:Proto-Oncogene Proteins B-raf