Cytosine deaminase-expressing human neural stem cells inhibit tumor growth in prostate cancer-bearing mice

Prostate cancer is the most common malignancy among men. Prostate cancer-related deaths are largely attributable to the development of hormone resistance in the tumor. No effective chemotherapy has yet been developed for advanced prostate cancer. It is desirable if a drug can be delivered directly and specifically to prostate cancer cells. Stem cells have selective migration ability toward cancer cells and therapeutic genes can be easily transduced into stem cells. In one form of gene therapy for cancer, the stem cells carry a gene encoding an enzyme that transforms an inert prodrug into a toxic product. Cytosine deaminase (CD) transforms the pro-drug 5-fluorocytosine into highly cytotoxic 5-fluorouracil (5-FU). The migration of the genetically modified stem cells was monitored by molecular magnetic resonance imaging, after labeling the stem cells with fluorescent magnetic nanoparticles (MNPs). Human neural stem cells encoding CD (HB1.F3.CD) were prepared and labeled with MNP. In tumor-bearing C57B mice, systemically transplanted HB1.F3.CD stem cells migrated toward the tumor and in combination with prodrug 5-FC, the volume of tumor implant was significantly reduced. These findings may contribute to development of a new selective chemotherapeutic strategy against prostate cancer.

► No effective chemotherapy has yet been developed for advanced prostate cancer. ► Stem cells have selective migration ability toward cancer and therapeutic genes can be readily transduced into stem cells. ► Human neural stem cells were labeled with nanoparticles and systematically transplanted in mice bearing prostate cancer. ► Transplanted stem cells encoding cytosine deaminase migrated selectively toward the tumor. ► In combination with prodrug 5-fluorocytosine, the tumor burden was significantly reduced.