An orthotopic model of anaplastic thyroid carcinoma in athymic nude mice.
OBJECTIVE
To develop an orthotopic model of anaplastic thyroid carcinoma (ATC) in athymic nude mice.


METHODS
Various thyroid carcinoma cell lines were injected into the thyroid gland of athymic nude mice to determine whether such injection was technically feasible. ATC cells were then injected into the thyroid gland or the subcutis of nude mice at various concentrations, and the mice were then followed for tumor development. The tumors were examined histopathologically for local invasion or regional or distant metastasis.


RESULTS
Injection of tumor cells into the thyroid glands of nude mice was technically feasible and resulted in the formation of thyroid tumors. The ATC cell line DRO showed significantly higher tumorigenicity in the thyroid gland than in the subcutis. In contrast, oral squamous cell carcinoma cell line TU167 shows no significantly higher tumorigenicity in the thyroid gland than in the subcutis. ATC tumors established in the thyroid gland also produced symptomatic compression of the esophagus and the trachea. Local invasion of the larynx and trachea was as well as high rates of pulmonary metastasis were also observed. Immunohistochemical staining showed higher microvessel density as well as higher expression of vascular endothelial growth factor and interleukin-8 in the orthotopic thyroid tumors than in ectopic tumors.


CONCLUSIONS
An orthotopic model of ATC in athymic nude mice was developed that closely recapitulates the clinical findings of human ATC. This model should facilitate the understanding of the pathogenesis of ATC and aid in the development of novel therapies against ATC.
Kim
Seungwon
S
Department of Head and Neck Surgery, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA.
Park
Young-Wook
YW
Schiff
Bradley A
BA
Doan
Dao D
DD
Yazici
Yasemin
Y
Jasser
Samar A
SA
Younes
Maher
M
Mandal
Mahitosh
M
Bekele
Benjamin N
BN
Myers
Jeffrey N
JN
D000818:Animals; D002277:Carcinoma / Q000473:pathology* / Q000662:veterinary*; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D013964:Thyroid Neoplasms / Q000473:pathology* / Q000662:veterinary*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured