Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2016) 41 EP639 | DOI: 10.1530/endoabs.41.EP639

ECE2016 Eposter Presentations Endocrine tumours and neoplasia (68 abstracts)

Effects of genetically engineered human neural stem cells expressing cytosine deaminase and interferon-beta on the growth of lymph node metastatic colorectal adenocarcinoma

Geon-Tae Park & Kyung-Chul Choi


Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea.


Genetically engineered stem cells may be advantageous for gene therapy against various human cancers due to their inherent tumor-tropic properties. In this study, we employed human neural stem cells (HB1.F3; hNSCs) transduced with genes expressing Escherichia coli cytosine deaminase (HB1.F3.CD) and human interferon-beta (HB1.F3.CD.IFN-β) as a treatment strategy for human lymph node metastatic colorectal cancer. CD can convert the prodrug 5-fluorocytosine (5-FC) to its active chemotherapeutic form, 5-fluorouracil (5-FU), which induces a tumor-killing effect through DNA synthesis inhibition. IFN-β also slightly inhibits tumor growth by inducing apoptotic process. In RT-PCR analysis, we confirmed that HB1.F3.CD cells expressed CD gene and HB1.F3.CD.IFN-β cells expressed both CD and IFN-β genes. A modified transwell migration assay showed that HB1.F3.CD and HB1.F3.CD.IFN-β cells selectively migrated toward SW-620 human lymph node metastatic colorectal cancer cells. When co-cultured with HB1.F3.CD or HB1.F3.CD.IFN-β cells in the presence of 5-FC, the viability of SW-620 cells were significantly reduced. In a xenografted mouse model, hNSCs treatment significantly inhibited the growth of tumor mass and the expression of proliferative marker without any harmful effects on the animals. In addition, fluorescent-labeled hNSCs could be found in the excised tumor mass. The tumor-tropic properties of these engineered hNSCs were found to be attributed to chemoattractant factors secreted by SW-620 cells, SDF-1, c-kit, uPAR, uPA and CCR2. Consequently, the present results represent that engineered hNSCs and prodrug treatment inhibits the growth of human lymph node metastatic colorectal cancer. Therefore, hNSC therapy may be a clinically effective tool for the treatment of human lymph node metastatic colorectal cancer.

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