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.

Genetically engineered stem cells may be advantageous for gene therapy against various human cancers due to their inherent tumor-tropic properties. In this study, genetically engineered human neural stem cells (HB1.F3) expressing Escherichia coli cytosine deaminase (HB1.F3.CD) and human interferon-β (HB1.F3.CD.IFN-β) were employed against lymph node-derived metastatic colorectal adenocarcinoma. CD can convert a prodrug, 5-fluorocytosine (5-FC), to active 5-fluorouracil (5-FU), which inhibits tumor growth through the inhibition of DNA synthesis, while IFN-β also strongly inhibits tumor growth by inducing the apoptotic process. In RT-PCR analysis, we confirmed that HB1.F3.CD cells expressed the CD gene and HB1.F3.CD.IFN-β cells expressed both CD and IFN-β genes. In results of a modified trans-well migration assay, HB1.F3.CD and HB1.F3.CD.IFN-β cells selectively migrated toward SW-620, human lymph node-derived metastatic colorectal adenocarcinoma cells. The viability of SW-620 cells was significantly reduced when co-cultured with HB1.F3.CD or HB1.F3.CD.IFN-β cells in the presence of 5-FC. In addition, it was found that the tumor-tropic properties of these engineered hNSCs were attributed to chemoattractant molecules including s SDF-1, c-kit, uPAR, uPA and CCR2s secreted by SW-620 cells. In a xenograft mouse model, treatment with hNSC resulted in significantly inhibited growth of the tumor mass without virulent effects on the animals. The current results indicate that engineered hNSCs and a prodrug treatment inhibited the growth of SW-620 cells. Therefore, hNSC therapy may be a clinically effective tool for the treatment of lymph node metastatic colorectal cancer.

Citation

Geon-Tae Park, Seung U Kim, Kyung-Chul Choi. 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 research and treatment : official journal of Korean Cancer Association. 2016 May 3

PMID: 27188205

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