Methodology, Criteria, and Characterization of Patient-Matched Thyroid Cell Lines and Patient-Derived Tumor Xenografts. J Clin Endocrinol Metab 2018 Sep 01;103(9):3169-3182
Date
05/31/2018Pubmed ID
29846633Pubmed Central ID
PMC6126888DOI
10.1210/jc.2017-01845Scopus ID
2-s2.0-85054142148 (requires institutional sign-in at Scopus site) 9 CitationsAbstract
OBJECTIVE: To investigate the molecular underpinnings of thyroid cancer, preclinical cell line models are crucial; however, ∼40% of these have been proven to be either duplicates of existing thyroid lines or even nonthyroid-derived lines or are not derived from humans at all. Therefore, we set out to establish procedures and guidelines that should proactively avoid these problems, which facilitated the creation of criteria to make valid preclinical models for thyroid cancer research.
DESIGN: Based on our recommendations, we systematically characterized all new cell lines that we generated by a standardized approach that included (1) determination of human origin, (2) exclusion of lymphoma, (3) DNA fingerprinting and histological comparisons to establish linkage to presumed tissue of origin, (4) examining thyroid differentiation by screening two to three thyroid markers, (5) examination of biological behavior (growth rate, tumorigenicity), and (6) presence of common thyroid cancer genetic changes (TP53, BRAF, PTEN, PIK3CA, RAS, TERT promoter, RET/PTC, PAX8/PPARγ, NF1, and EIF1AX).
RESULTS: We established seven new thyroid cell lines (LAM136, EAM306, SDAR1, SDAR2, JEM493, THJ529, and THJ560) out of 294 primary culture attempts, and 10 patient-derived tumor xenografts (PDTXs; MC-Th-95, MC-Th-374, MC-Th-467, MC-Th-491, MC-Th-493, MC-Th-504, MC-Th-524, MC-Th-529, MC-Th-560, and MC-Th-562) out of 67 attempts. All were successfully validated by our protocols.
CONCLUSIONS: This standardized approach for cell line and PDTX characterization should prevent (or detect) future cross-contamination and ensure that only valid preclinical models are used for thyroid cancer research.
Author List
Marlow LA, Rohl SD, Miller JL, Knauf JA, Fagin JA, Ryder M, Milosevic D, Netzel BC, Grebe SK, Reddi HV, Smallridge RC, Copland JAMESH terms used to index this publication - Major topics in bold
AgedAged, 80 and over
Animals
Cell Differentiation
Cell Division
Cell Line, Tumor
Cell Transformation, Neoplastic
DNA Fingerprinting
DNA, Neoplasm
Female
Heterografts
Humans
Male
Mice, Nude
Middle Aged
Mutation
Neoplasm Transplantation
Thyroid Neoplasms
Tumor Cells, Cultured