Antithyroid cancer effects of human neural stem cells expressing therapeutic genes on anaplastic thyroid cancer cells. Issue 2 (12th September 2019)

• Record Type: Journal Article
• Authors: Shin, Hye‐Ji; Hwang, Kyung‐A.; Go, Ryeo‐Eun; Kim, Seung U.; Choi, Kyung‐Chul
• Is Part Of: Journal of cellular biochemistry. Volume 121:Issue 2(2020)
• Page Start: 1586
• Page End: 1598
• Publication Date: 2019-09-12
• Subjects: anaplastic thyroid cancer -- cytosine deaminase -- interferon‐β -- neural stem cells -- reactive oxygen species; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.29393
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Stem cells that express therapeutic proteins have been identified to have an anticancer effects on various types of cancer. In the present study study, human neural stem cells (hNSCs) that were genetically engineered to express cytosine deaminase (CD) and human interferon‐β (IFN‐β) were used for anaplastic thyroid cancer (ATC) treatment owing to their tumor‐tropic properties and therapeutic effects. CD is an enzyme that converts 5‐fluorocytosine (5‐FC), a prodrug, to 5‐fluorouracil (5‐FU) which is a medication to suppress tumor growth through DNA synthesis inhibition. Also, IFN‐β suppresses tumor growth by the induction of apoptotic process. In water soluble tetrazolium salt (WST) assay, SNU‐80 cells which are human female ATC cells were cocultured with three cell types including engineered hNSCs such as HB1.F3, HB1.F3.CD, and HB1.F3.CD.IFN‐β cells on transwells and treated with 5‐FC for 72 hours. Finally, the SNU‐80 cell viability was reduced by the coculture with HB1.F3.CD and HB1.F3.CD.IFN‐β cells. In dichlorofluorescein diacetate (DCF‐DA) and TdT‐mediated dUTP nick‐end labeling (TUNEL) assays, the production of reactive oxygen species (ROS) and the number of apoptotic cells were increased by HB1.F3.CD and HB1.F3.CD.IFN‐β cells in the presence of 5‐FC. In Western blot assay, ROS, and apoptosis‐related genes were increased in SNU‐80 cells when they were cocultured with HB1.F3.CD and HB1.F3.CD.IFN‐β cells. In transwell migration assay, hNSCs selectively migrated to SNU‐80 cells because hNSCs interacted with chemoattractant factors like SDF‐1α, uPAR, and CCR2 secreted by SNU‐80 cells. Taken together, engineered hNSCs were revealed to selectively migrate to ATC cells and to inhibit growth as well as to induce apoptosis of ATC cells via ROS production through the actions of transgenes such as CD and IFN‐β. Therefore, these engineered hNSCs can be promising candidates for the treatment of metastatic ATC. Abstract : These stem cells migrated to SNU‐80 cells due to chemoattractant factors like SDF‐1α, uPAR, and CCR2. Engineered human neural stem cells can be used as an alternative therapeutic tool to treat metastatic anaplastic thyroid cancer.