Suppression of the growth of human colorectal cancer cells by therapeutic stem cells expressing cytosine deaminase and interferon-β via their tumor-tropic effect in cellular and xenograft mouse models
| Autor: | Kyung-Chul Choi, Min-Ah Park, Nam-Hee Kang, Bo-Rim Yi, Hye-Rim Lee, Kelvin J. Choi, Seung U. Kim |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Antimetabolites Antineoplastic Cancer Research Colon Biology Cell Line Cytosine Deaminase Mice Cancer stem cell Cell Line Tumor Escherichia coli Genetics medicine Animals Humans Cytotoxic T cell Cell Engineering Mice Inbred BALB C Stem Cells Cytosine deaminase Rectum Cancer Genetic Therapy Interferon-beta General Medicine medicine.disease Molecular biology Neural stem cell Oncology Cell culture Papers Cancer cell Molecular Medicine Fluorouracil Stem cell Colorectal Neoplasms Stem Cell Transplantation |
| Zdroj: | Molecular Oncology. 7:543-554 |
| ISSN: | 1574-7891 |
| DOI: | 10.1016/j.molonc.2013.01.004 |
| Popis: | Genetically engineered stem cells (GESTECs) exhibit a potent therapeutic efficacy via their strong tumor tropism toward cancer cells. In this study, we introduced the human parental neural stem cells, HB1.F3, with the human interferon beta (IFN-β) gene which is a typical cytokine gene that has an antitumor effect and the cytosine deaminase (CD) gene from Escherichia coli (E. coli) that could convert the non-toxic prodrug, 5-fluorocytosine (5-FC), to a toxic metabolite, 5-fluorouracil (5-FU). Two types of stem cells expressing the CD gene (HB1.F3.CD cells) and both the CD and human IFN-β genes (HB1.F3.CD.IFN-β) were generated. The present study was performed to examine the migratory and therapeutic effects of these GESTECs against the colorectal cancer cell line, HT-29. When co-cultured with colorectal cancer cells in the presence of 5-FC, HB1.F3.CD and HB1.F3.CD.IFN-β cells exhibited the cytotoxicity on HT-29 cells via the bystander effect. In particular, HB1.F3.CD.IFN-β cells showed the synergistic cytotoxic activity of 5-FU and IFN-β. We also confirmed the migration ability of HB1.F3.CD and HB1.F3.CD.IFN-β cells toward HT-29 cells by a modified migration assay in vitro, where chemoattractant factors secreted by HT-29 cells attracted the GESTECs. In a xenograft mouse model, the volume of tumor mass was decreased up to 56% in HB1.F3.CD injected mice while the tumor mass was greatly inhibited about 76% in HB1.F3.CD.IFN-β injected mice. The therapeutic treatment by these GESTECs is a novel strategy where the combination of the migration capacity of stem cells as a vector for therapeutic genes towards colorectal cancer and a synergistic antitumor effect of CD and IFN-β genes can selectively target this type of cancer. |
| Databáze: | OpenAIRE |
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