Platelet-derived growth factor receptor-α subunit targeting suppresses metastasis in advanced thyroid cancer in vitro and in vivo

Ching Ling Lin, Ming Lin Tsai, Yu Hsin Chen, Wei Ni Liu, Chun Yu Lin, Kai Wen Hsu, Chien Yu Huang, Yu Jia Chang, Po Li Wei, Shu Huey Chen, Li Chi Huang, Chia Hwa Lee

研究成果: 雜誌貢獻文章同行評審

2 引文 斯高帕斯(Scopus)

摘要

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

原文英語
頁(從 - 到)551-561
頁數11
期刊Biomolecules and Therapeutics
29
發行號5
DOIs
出版狀態已發佈 - 9月 2021

ASJC Scopus subject areas

  • 生物化學
  • 分子醫學
  • 藥理
  • 藥物發現

指紋

深入研究「Platelet-derived growth factor receptor-α subunit targeting suppresses metastasis in advanced thyroid cancer in vitro and in vivo」主題。共同形成了獨特的指紋。

引用此