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Novel three-dimensional cultures provide insights into thyroid cancer behavior.
Authors Lee MA, Bergdorf KN, Phifer CJ, Jones CY, Byon SY, Sawyer LM, Bauer JA, Weiss VL
Submitted By Submitted Externally on 9/28/2020
Status Published
Journal Endocrine-related cancer
Year 2020
Date Published 2/1/2020
Volume : Pages 27 : 111 - 121
PubMed Reference 31804972
Abstract Thyroid cancer has the fastest growing incidence of any cancer in the United
States, as measured by the number of new cases per year. Despite advances in
tissue culture techniques, a robust model for thyroid cancer spheroid culture is
yet to be developed. Using eight established thyroid cancer cell lines, we
created an efficient and cost-effective 3D culture system that can enhance our
understanding of in vivo treatment response. We found that all eight cell lines
readily form spheroids in culture with unique morphology, size, and cytoskeletal
organization. In addition, we developed a high-throughput workflow that allows
for drug screening of spheroids. Using this approach, we found that spheroids
from K1 and TPC1 cells demonstrate significant differences in their
sensitivities to dabrafenib treatment that closely model expected patient drug
response. In addition, K1 spheroids have increased sensitivity to dabrafenib
when compared to monolayer K1 cultures. Utilizing traditional 2D cultures of
these cell lines, we evaluated the mechanisms of this drug response, showing
dramatic and acute changes in their actin cytoskeleton as well as inhibition of
migratory behavior in response to dabrafenib treatment. Our study is the first
to describe the development of a robust spheroid system from established
cultured thyroid cancer cell lines and adaptation to a high-throughput format.
We show that combining 3D culture with traditional 2D methods provides a
complementary and powerful approach to uncover drug sensitivity and mechanisms
of inhibition in thyroid cancer.


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