Pancreatic tumor mass in a xenograft mouse model is decreased by treatment with therapeutic stem cells following introduction of therapeutic genes

Pancreatic cancer is the fourth most common cause of cancer-related mortality. In the present study, we employed 2 types of therapeutic stem cells expressing cytosine deaminase (CD) with or without human interferon-β (IFN-β), HB1.F3.CD and HB1.F3.CD.IFN-β cells, respectively, to selectively treat pancreatic cancer. The CD gene converts the non-toxic prodrug, 5-flurorocytosine (5-FC), into the toxic agent, 5-fluorouracil (5-FU). In addition, human IFN-β is a potent cytokine that has antitumor effects. To generate a xenograft mouse model, PANC-1 cells (2×106/mouse) cultured in DMEM containing 10% FBS were mixed with Matrigel and were subcutaneously injected into BALB/c nu/nu mice. In the migration assay, the stem cells expressing the CD or IFN-β gene effectively migrated toward the pancreatic cancer cells, suggesting the presence of chemoattractant factors secreted by the pancreatic tumors. In the co-culture and MTT assay, antitumor activity of the therapeutic stem cells was observed in the presence of 5-FC was shown that the growth of PANC-1 cells was inhibited. Furthermore, these effects were confirmed in the xenograft mouse model bearing tumors originating from PANC-1 cells. Analyses by histological and fluorescence microscopy showed that treatment with the stem cells resulted in the inhibition of pancreatic cancer growth in the presence of 5-FC. Taken together, these results indicate that stem cells expressing the CD and/or IFN-β gene can be used to effectively treat pancreatic cancer and reduce the side-effects associated with conventional therapies.