Thyroid cancer is the most common endocrine
malignancy and is predicted to be the 4th most commonly diagnosed cancer by
2030. Approximately one-half of follicular thyroid carcinomas (FTC) contain
genetic alterations in RAS family members.
Furthermore, Cowden’s
disease, which is characterized by loss of PTEN, predisposes for the
development of FTC in humans. We have shown that thyroid specific expression of
HrasG12V at endogenous levels and Pten inactivation (HrasG12V/Pten-/-/TPO-cre
mice) leads to the development of FTCs that closely recapitulate human disease,
with complete penetrance at one year.
In patients, FTCs metastasize via the
bloodstream to distant sites, frequently the lungs, bones and brain. The first
objective of the study was to determine if these mice developed de novo
metastasis to relevant sites. Indeed, spontaneous metastasis to the lungs was
observed in 56% of HrasG12V/ Pten-/-/TPO-cre mice. We next sought to identify
the cellular components within the tumor microenvironment (TME) of FTC that
contribute to tumor progression and metastasis via FACS analysis.
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