1. Academic Validation
  2. Organoid Cultures Derived From Patients With Papillary Thyroid Cancer

Organoid Cultures Derived From Patients With Papillary Thyroid Cancer

  • J Clin Endocrinol Metab. 2021 Apr 23;106(5):1410-1426. doi: 10.1210/clinem/dgab020.
Dong Chen 1 2 Yawen Tan 3 Zhichao Li 1 Wujiao Li 1 Lei Yu 1 Wei Chen 1 Yuchen Liu 1 Lisa Liu 1 Liangfeng Guo 3 Weiren Huang 1 2 Yongsheng Zhao 1 4
Affiliations

Affiliations

  • 1 Institute of Shenzhen Translational Medicine, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China.
  • 2 Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China.
  • 3 Department of Breast and Thyroid Surgery, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.
  • 4 Department of Nuclear Medicine, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China.
Abstract

Context: Papillary thyroid Cancer (PTC) has been one of the most frequent endocrine malignancies around the world. Although most PTC patients have a favorable prognosis, a subgroup of patients die, especially when disease recurrence occurs. There is a pressing need for clinically relevant preclinical thyroid Cancer models for personalized therapy because of the lack of in vitro models that faithfully represent the biology of the parental tumors.

Objective: To understand thyroid Cancer and translate this knowledge to clinical applications, patient-derived PTC organoids as a promising new preclinical model were established.

Methods: Surgically resected PTC primary tissues were dissociated and processed for organoid derivation. Tumor organoids were subsequently subjected to histological characterization, DNA sequencing, drug screen, and cell proliferation assay, respectively.

Results: We describe a 3-dimensional culture system for the long-term expansion of patient-derived PTC organoid lines. Notably, PTC organoids preserve the histopathological profiles and genomic heterogeneity of the originating tumors. Drug sensitivity assays of PTC organoids demonstrate patient-specific drug responses, and large correlations with the respective mutational profiles. Estradiol was shown to promote cell proliferation of PTC organoids in the presence of Estrogen Receptor α (ERα), regardless of the expression of ERβ and G protein-coupled ER.

Conclusion: These data suggest that these newly developed PTC-derived organoids may be an excellent preclinical model for studying clinical response to anticancer drugs in a personalized way, as well as provide a potential strategy to develop prevention and treatment options for thyroid Cancer with ERα-specific antagonists.

Keywords

drug screen; estradiol; estrogen receptor α; genetic heterogeneity; organoid; papillary thyroid cancer.

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