A Novel Orthotopic Mouse Model of Human Anaplastic Thyroid Carcinoma

被引:69
作者
Nucera, Carmelo [1 ]
Nehs, Matthew A. [1 ]
Mekel, Michal [1 ]
Zhang, Xuefeng [2 ]
Hodin, Richard [1 ]
Lawler, Jack [2 ]
Nose, Vania [3 ]
Parangi, Sareh [1 ]
机构
[1] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Thyroid Canc Res Lab,Unit Endocrine Surg, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Canc Biol & Angiogenesis,Dept Pathol, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
GROWTH-FACTOR RECEPTOR; ATHYMIC NUDE-MICE; TRANSCRIPTION FACTORS; CANCER PROGRESSION; TRANSGENIC MICE; DRUG-EVALUATION; CELL-LINES; INHIBITION; XENOGRAFTS; EXPRESSION;
D O I
10.1089/thy.2009.0055
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1077 / 1084
页数:8
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