Interest in gene therapy has recently increased; in particular, gene-directed
enzyme/
prodrug therapies have been found to be more advantageous compared to
radiotherapy and/or
chemotherapy. One of these, a
cytosine deaminase (CD)/5-fluorocytosine (5-FC) system, is known to induce apoptosis by converting 5-FC, a
prodrug, to its metabolically active form,
5-fluorouracil. The present study was designed to examine the migratory and
therapeutic effects of engineered human stem cell lines against
endometrial cancer using this strategy. The parental stem cells, HB1.F3, were modified to express Escherichia coli CD or human
interferon-beta (IFN-β), thereby producing HB1.F3.CD and HB1.F3.CD.IFN-β cells, respectively. The parental and engineered stem cells (HB1.F3, HB1.F3.CD, and HB1.F3.CD.IFN-β) significantly migrated toward
endometrial cancer cells (Ishikawa) more than primary bovine fibroblasts (bovine FB). In addition, important
chemoattractant factors, including
stem cell factor (SCF), vescular
endothelial growth factor, vescular
endothelial growth factor receptor 2,
C-X-C chemokine receptor type 4, and c-KIT, involved in the
tumor-tropic ability of stem cells were expressed in Ishikawa cells. In using a co-culture system and MTT assay, reduced viability of
endometrial cancer cells was observed in the presence of HB1.F3.CD and HB1.F3.CD.IFN-β cells with
prodrug 5-FC. Taken together, these results suggest that gene therapy employing genetically modified stem cells expressing CD and IFN-β may be effective for treating
endometrial cancer.