Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
June-2020 Volume 43 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
June-2020 Volume 43 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

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
  • View Affiliations / Copyright

    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
  • Pages: 2045-2052
    |
    Published online on: March 30, 2020
       https://doi.org/10.3892/or.2020.7570
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



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.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Williams RT, Yu AL, Diccianni MB, Theodorakis EA and Batova A: Renal cancer-selective englerin A induces multiple mechanisms of cell death and autophagy. J Exp Clin Cancer Res. 32:572013. View Article : Google Scholar :

2 

Curti BD: Renal cell carcinoma. JAMA. 292:97–100. 2004. View Article : Google Scholar

3 

Gupta K, Miller JD, Li JZ, Russell MW and Charbonneau C: Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): A literature review. Cancer Treat Rev. 34:193–205. 2008. View Article : Google Scholar

4 

Basu B and Eisen T: Perspectives in drug development for metastatic renal cell cancer. Target Oncol. 5:139–156. 2010. View Article : Google Scholar

5 

Saini S, Liu J, Yamamura S, Majid S, Kawakami K, Hirata H and Dahiya R: Functional significance of secreted frizzled-related protein 1 in metastatic renal cell carcinomas. Cancer Res. 69:6815–6822. 2009. View Article : Google Scholar

6 

Matias M, Casa-Nova M, Borges-Costa J and Ribeiro L: Unusual head metastasis of kidney cancer. BMJ Case Rep. 2013:bcr20132000042013. View Article : Google Scholar :

7 

Zhang F, Shang D, Zhang Y and Tian Y: Interleukin-22 suppresses the growth of A498 renal cell carcinoma cells via regulation of STAT1 pathway. PLoS One. 6:e203822011. View Article : Google Scholar :

8 

Amato RJ: Renal cell carcinoma: Review of novel single-agent therapeutics and combination regimens. Ann Oncol. 16:7–15. 2005. View Article : Google Scholar

9 

Lane BR, Rini BI, Novick AC and Campbell SC: Targeted molecular therapy for renal cell carcinoma. Urology. 69:3–10. 2007. View Article : Google Scholar

10 

Antonelli A, Cozzoli A, Zani D, Zanotelli T, Nicolai M, Cunico SC and Simeone C: The follow-up management of non-metastatic renal cell carcinoma: Definition of a surveillance protocol. BJU Int. 99:296–300. 2007. View Article : Google Scholar

11 

Huber BE, Austin EA, Richards CA, Davis ST and Good SS: Metabolism of 5-fluorocytosine to 5-fluorouracil in human colorectal tumor cells transduced with the cytosine deaminase gene: Significant antitumor effects when only a small percentage of tumor cells express cytosine deaminase. Proc Natl Acad Sci USA. 91:8302–8306. 1994. View Article : Google Scholar

12 

Nawa A, Tanino T, Luo C, Iwaki M, Kajiyama H, Shibata K, Yamamoto E, Ino K, Nishiyama Y and Kikkawa F: Gene directed enzyme prodrug therapy for ovarian cancer: Could GDEPT become a promising treatment against ovarian cancer? Anticancer Agents Med Chem. 8:232–239. 2008. View Article : Google Scholar

13 

Qiao J, Doubrovin M, Sauter BV, Huang Y, Guo ZS, Balatoni J, Akhurst T, Blasberg RG, Tjuvajev JG, Chen SH and Woo SL: Tumor-specific transcriptional targeting of suicide gene therapy. Gene Ther. 9:168–175. 2002. View Article : Google Scholar

14 

Ye L, Tao K, Yu Y and Wang G: Reduction of G0 phase cells of colon cancer caco-2 cells may enhance 5-fluorouracil efficacy. J Biomed Res. 24:64–68. 2010. View Article : Google Scholar :

15 

Kim KY, Kim SU, Leung PC, Jeung EB and Choi KC: Influence of the prodrugs 5-fluorocytosine and CPT-11 on ovarian cancer cells using genetically engineered stem cells: Tumor-tropic potential and inhibition of ovarian cancer cell growth. Cancer Sci. 101:955–962. 2010. View Article : Google Scholar

16 

Yi BR, Kang NH, Hwang KA, Kim SU, Jeung EB and Choi KC: Antitumor therapeutic effects of cytosine deaminase and interferon-β against endometrial cancer cells using genetically engineered stem cells in vitro. Anticancer Res. 31:2853–2861. 2011.

17 

Garrison JI, Berens ME, Shapiro JR, Treasurywala S and Floyd-Smith G: Interferon-beta inhibits proliferation and progression through S phase of the cell cycle in five glioma cell lines. J Neurooncol. 30:213–223. 1996. View Article : Google Scholar

18 

Ren C, Kumar S, Chanda D, Kallman L, Chen J, Mountz JD and Ponnazhagan S: Cancer gene therapy using mesenchymal stem cells expressing interferon-beta in a mouse prostate cancer lung metastasis model. Gene Ther. 15:1446–1453. 2008. View Article : Google Scholar :

19 

Kim SU, Nakagawa E, Hatori K, Nagai A, Lee MA and Bang JH: Production of immortalized human neural crest stem cells. Methods Mol Biol. 198:55–65. 2002.

20 

Jeong SW, Chu K, Jung KH, Kim SU, Kim M and Roh JK: Human neural stem cell transplantation promotes functional recovery in rats with experimental intracerebral hemorrhage. Stroke. 34:2258–2263. 2003. View Article : Google Scholar

21 

Kim GS, Heo JR, Kim SU and Choi KC: Cancer-Specific inhibitory effects of genetically engineered stem cells expressing cytosine deaminase and interferon-β against choriocarcinoma in xenografted metastatic mouse models. Transl Oncol. 11:74–85. 2017. View Article : Google Scholar :

22 

Park GT, Kim SU and Choi KC: Anti-proliferative effect of engineered neural stem cells expressing cytosine deaminase and interferon-β against lymph node-derived metastatic colorectal adenocarcinoma in cellular and xenograft mouse models. Cancer Res Treat. 9:79–91. 2017. View Article : Google Scholar

23 

Kim SU, Jeung EB, Kim YB, Cho MH and Choi KC: Potential tumor-tropic effect of genetically engineered stem cells expressing suicide enzymes to selectively target invasive cancer in animal models. Anticancer Res. 31:1249–1258. 2011.

24 

Li C, Penet MF, Winnard P Jr, Artemov D and Bhujwalla ZM: Image-guided enzyme/prodrug cancer therapy. Clin Cancer Res. 14:515–522. 2008. View Article : Google Scholar

25 

Singer EA, Gupta GN, Marchalik D and Srinivasan R: Evolving therapeutic targets in renal cell carcinoma. Curr Opin Oncol. 25:273–280. 2013. View Article : Google Scholar

26 

Schwartz MJ, Liu H, Hwang DH, Kawamoto H and Scherr DS: Antitumor effects of an imidazoquinoline in renal cell carcinoma. Urology. 73:1156–1162. 2009. View Article : Google Scholar

27 

Lam JS, Leppert JT, Belldegrun AS and Figlin RA: Novel approaches in the therapy of metastatic renal cell carcinoma. World J Urol. 23:202–212. 2005. View Article : Google Scholar

28 

Lash GE, Warren AY, Underwood S and Baker PN: Vascular endothelial growth factor is a chemoattractant for trophoblast cells. Placenta. 24:549–556. 2003. View Article : Google Scholar

29 

Koshiba T, Hosotani R, Miyamoto Y, Ida J, Tsuji S, Nakajima S, Kawaguchi M, Kobayashi H, Doi R, Hori T, et al: Expression of stromal cell-derived factor 1 and CXCR4 ligand receptor system in pancreatic cancer: A possible role for tumor progression. Clin Cancer Res. 6:3530–3535. 2000.

30 

Yi BR, O SN, Kang NH, Hwang KA, Kim SU, Jeung EB, Kim YB, Heo GJ and Choi KC: Genetically engineered stem cells expressing cytosine deaminase and interferon-β migrate to human lung cancer cells and have potentially therapeutic anti-tumor effects. Int J Oncol. 39:833–839. 2011.

31 

Zhao D, Najbauer J, Garcia E, Metz MZ, Gutova M, Glackin CA, Kim SU and Aboody KS: Neural stem cell tropism to glioma: Critical role of tumor hypoxia. Mol Cancer Res. 6:1819–1829. 2008. View Article : Google Scholar

32 

Fischer UM, Harting MT, Jimenez F, Monzon-Posadas WO, Xue H, Savitz SI, Laine GA and Cox CS Jr: Pulmonary passage is a major obstacle for intravenous stem cell delivery: The pulmonary first-pass effect. Stem Cells Dev. 18:683–692. 2009. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Kim GS, Kim SM, Kim SU, Lee G and Choi KC: Inhibitory effect of therapeutic genes, cytosine deaminase and interferon‑β, delivered by genetically engineered stem cells against renal cell carcinoma. Oncol Rep 43: 2045-2052, 2020.
APA
Kim, G., Kim, S., Kim, S.U., Lee, G., & Choi, K. (2020). Inhibitory effect of therapeutic genes, cytosine deaminase and interferon‑β, delivered by genetically engineered stem cells against renal cell carcinoma. Oncology Reports, 43, 2045-2052. https://doi.org/10.3892/or.2020.7570
MLA
Kim, G., Kim, S., Kim, S. U., Lee, G., Choi, K."Inhibitory effect of therapeutic genes, cytosine deaminase and interferon‑β, delivered by genetically engineered stem cells against renal cell carcinoma". Oncology Reports 43.6 (2020): 2045-2052.
Chicago
Kim, G., Kim, S., Kim, S. U., Lee, G., Choi, K."Inhibitory effect of therapeutic genes, cytosine deaminase and interferon‑β, delivered by genetically engineered stem cells against renal cell carcinoma". Oncology Reports 43, no. 6 (2020): 2045-2052. https://doi.org/10.3892/or.2020.7570
Copy and paste a formatted citation
x
Spandidos Publications style
Kim GS, Kim SM, Kim SU, Lee G and Choi KC: Inhibitory effect of therapeutic genes, cytosine deaminase and interferon‑β, delivered by genetically engineered stem cells against renal cell carcinoma. Oncol Rep 43: 2045-2052, 2020.
APA
Kim, G., Kim, S., Kim, S.U., Lee, G., & Choi, K. (2020). Inhibitory effect of therapeutic genes, cytosine deaminase and interferon‑β, delivered by genetically engineered stem cells against renal cell carcinoma. Oncology Reports, 43, 2045-2052. https://doi.org/10.3892/or.2020.7570
MLA
Kim, G., Kim, S., Kim, S. U., Lee, G., Choi, K."Inhibitory effect of therapeutic genes, cytosine deaminase and interferon‑β, delivered by genetically engineered stem cells against renal cell carcinoma". Oncology Reports 43.6 (2020): 2045-2052.
Chicago
Kim, G., Kim, S., Kim, S. U., Lee, G., Choi, K."Inhibitory effect of therapeutic genes, cytosine deaminase and interferon‑β, delivered by genetically engineered stem cells against renal cell carcinoma". Oncology Reports 43, no. 6 (2020): 2045-2052. https://doi.org/10.3892/or.2020.7570
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team