ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 GP85 | DOI: 10.1530/endoabs.63.GP85

Follistain-like 1 (Fstl1) may reduce metastastic activity of anaplastic thyroid cancer by increasging thyroid transcription factor 1 (TTF1) and epithelial gene markers

Jong Suk Park1, Arim Choi1, Jung Hye Kim1, Kahui Park1, Sang Bae Lee1, YuSik Kim2, Ji Sun Nam1, Shinae Kang1 & Chul Woo Ahn1

1Division of Endocrinology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medcine, Seoul, Republic of Korea; 2Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul, Republic of Korea.

Background: Although anaplastic thyroid cancer (ATC) is found in less than 2% of patients with thyroid cancer, it is the most advanced, aggressive and lethal. ATC is known to develop from well-differentiated thyroid cancers, such as follicular thyroid cancer, and it is undifferentiated itself. Among the thyroid-specific transcription factors that are critical for the function of thyroid, the expression of thyroid transcription factor 1 (TTF1), or NKX2.1, has been reported to correlate with the degree of differentiation, thus, its level is the lowest in ATC among thyroid cancers. TTF1 was reported to reduce invasion and metastasis in lung cancer; however, its regulatory effects on metastasis in ATC in unknown. The metastasis suppression effect of follistatin-like 1 (Fstl1) has been recently reported; however, the results are inconsistent. Herein, we investigated the effects of Fstl1 on metastasis of ATC cell line.

Methods: 8505C cell line was maintained in EMEM containing 2 mM glutamine, 1% non-essential amino acids and 10% FBS. Human Fstl1 was treated at 200 ng/m for 24 hr, 48 hr, and 72 hr. Cell viability was measured by MTT assay. Expression of epithelial gene markers including claudin 1, claudin 4, claudin 7, and occludin and mesenchymal gene markers including vimentin and N-cadherin were confirmed by real-time quantitative PCR (qPCR). In addition, gene expression of TTF1 was also measured by qPCR. Protein expression of each marker was examined by western blot.

Results: Fstl1 did not affect cell viability. Gene expressions of claudin 1, 4 and 7 significantly increased after 24 hours compared to control while that of TTF1 significantly increased after 72 hours. However, there was no significant change in protein expression of each marker. None of mesenchymal markers were changed in response to Fstl1.

Conclusion: We demonstrated that Fstl1 increased epithelial gene markers and TTF1 in 8505C cell line. These suggest that Fstl1 can suppress metastastic activity of anaplastic thyroid cancer.