A Novel Orthotopic Mouse Model of Human Anaplastic Thyroid Carcinoma

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.

Theranostic near-infrared fluorescent nanoplatform for imaging and systemic siRNA delivery to metastatic anaplastic thyroid cancer

“…The aggressive orthotopic tumor model has been widely accepted as a more clinically relevant and better predictive model to assess the anticancer therapeutic efficacy of drug delivery systems based on the fact that tumor cells are implanted directly into the target organ, providing a tumor microenvironment with biological, invasive, and metastatic properties more similar to clinical cases (25). To further explore the potential applications of our NPs in ATC treatment, we conducted in vivo studies using an orthotopic model of ATC by injecting BRAF V600E -mutated 8505C cells directly into the thyroid of immunodeficiency SCID mice (26). All mice developed cancers with high proliferation and aggressive behavior similar to human ATC.…”

Cancer stem-like cells and thyroid cancer

“…Orthotopic transplantation simulates the microenvironment and metastatic patterns of human cancer much better than subcutaneous transplantation. Nucera et al (2009) describe a novel orthotopic thyroid cancer model using distinctive 8505c ATC cells that demonstrated the features of aggressive tumors. Another approach is to use tail vein injection which often leads to lung metastases.…”

Anaplastic thyroid cancer – an overview of genetic variations and treatment modalities

“…[66][67][68][69] In the recent past, a number of transgenic mice have been developed that mimic ATC in vivo [70][71][72][73] and serve as much more clinically relevant models for preclinical testing. These models have primarily been used to elucidate the hypothesis that ATCs arise as a progression from PTC or FTC due to hits to multiple signaling pathways and therefore provide the closest simulation environment reflective of direct in human testing.…”