Inhibitory effect of therapeutic genes, cytosine deaminase and interferon‑β, delivered by genetically engineered stem cells against renal cell carcinoma

Kim,Gyu‑Sik; Kim,Soo‑Min; Kim,Seung U.; Lee,Gabsang; Choi,Kyung‑Chul

doi:10.3892/or.2020.7570

Inhibitory effect of therapeutic genes, cytosine deaminase and interferon‑β, delivered by genetically engineered stem cells against renal cell carcinoma

Authors:
- Gyu‑Sik Kim
- Soo‑Min Kim
- Seung U. Kim
- Gabsang Lee
- Kyung‑Chul Choi
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Affiliations: Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC V6T 1Z1, Canada, Institute for Cell Engineering, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Published online on: March 30, 2020 https://doi.org/10.3892/or.2020.7570
Pages: 2045-2052

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Abstract

Although the effects of stem cells expressing anticancer genes on tumor growth have been demonstrated by many researchers in various types of cancer, relatively few studies have investigated their inhibitory effects on cancer metastasis. In the present study, we examined the inhibitory effects of cytosine deaminase (CD)/5‑fluorocytosine (5‑FC) and interferon‑β (IFN‑β) using genetically engineered neural stem cells (hNSCs) in a cellular and metastasis model of renal cell carcinoma (RCC). The CD/5‑FC method has the advantage of minimizing damage to normal tissues since it selectively targets cancer cells by the CD gene, which converts prodrug 5‑FC to the drug 5‑fluorouracil. Moreover, we used hNSCs as a tool to effectively deliver the anticancer genes to the tumor site. These stem cells are known to possess tumor‑tropism because of chemoattractant factors expressed in cancer cells. Therefore, we ascertained the expression of these factors in A498 cells, a cell line of RCC, and identified the A498‑specific migration ability of hNSCs. We also confirmed that the proliferation of A498 cells was significantly reduced by therapeutic hNSCs in the presence of 5‑FC. Furthermore, we established an A498 metastasis model. In the animal experiment, the weight of the lungs increased in response to cancer metastasis, but was normalized by hNSCs expressing CD and/or IFN‑β genes, while the incidence of liver metastasis was suppressed by the hNSCs. Overall, the results of this study demonstrate that stem cells expressing anticancer genes have the potential for use as an alternative to conventional therapy for metastatic cancer.

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