A Novel Orthotopic Mouse Model of Human Anaplastic Thyroid Carcinoma
- 1 October 2009
- journal article
- research article
- Published by Mary Ann Liebert Inc in Thyroid®
- Vol. 19 (10), 1077-1084
- https://doi.org/10.1089/thy.2009.0055
Abstract
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.Keywords
This publication has 38 references indexed in Scilit:
- BRAF mutations in anaplastic thyroid carcinoma: implications for tumor origin, diagnosis and treatmentLaboratory Investigation, 2004
- Inhibition of growth and invasive ability of melanoma by inactivation of mutated BRAF with lentivirus-mediated RNA interferenceOncogene, 2004
- Orthotopic models of cancer for preclinical drug evaluationEuropean Journal Of Cancer, 2004
- Genome-Wide Appraisal of Thyroid Cancer ProgressionThe American Journal of Pathology, 2002
- Selective activity of BS-RNase against anaplastic thyroid cancer.2001
- Expression of thyroid-specific transcription factors TTF-1 and PAX-8 in human thyroid neoplasms.1994
- Metastatic models of human cancer xenografted in the nude mouse: The importance of orthotopic transplantationJournal of Cellular Biochemistry, 1994
- Site-specific chemosensitivity of human small-cell lung carcinoma growing orthotopically compared to subcutaneously in SCID mice: the importance of orthotopic models to obtain relevant drug evaluation data.1993
- Role of p53 mutations in endocrine tumorigenesis: mutation detection by polymerase chain reaction-single strand conformation polymorphism.1992
- Importance of orthotopic transplantation procedures in assessing the effects of transfected genes on human tumor growth and metastasisCancer and Metastasis Reviews, 1991