Endocrine Abstracts

In this study, human neural stem cells (hNSCs) were used to cancer treatment strategy for anaplastic thyroid cancer (ATC) owing to their tumor tropic properties. Cytosine deaminase (CD) can convert a prodrug, 5-fluorocytosine (5-FC), to drug, 5-fluorouracil (5-FU), which inhibits tumor growth through DNA synthesis inhibition. Also, IFN-β expression suppresses tumor growth by apoptotic process. Then, we investigated tumor inhibition effect of hNSCs in vitro and in vivo. We currently studying on a xenograft in vivo model, SNU-80 cells (2.0×10⁷cells/mouse) were injected subcutaneously (s.c.) after mixed with 1:1 volume ratio of Matrigel (BD Biosciences, Bedford, MA, USA) into the back of the mice. When the tumor volume reached at 150–200 mm³, CM-DiI pre-labeled hNSCs were injected subcutaneously closed to the tumor mass. After SNU-80 cells and hNSCs injection, 5-FC (500 mg/kg per day) injected every day for 21 days to Intraperitoneal injection (i.p.). In trans-well migration assay, HB1.F3.CD and HB1.F3.CD.IFN-β cells selectively migrated to SNU-80 cells because of its tumor-tropic properties. Engineering NSCs were attributed to chemo attractant factors like uPAR, CXCR4, SCF and VEGFR2 secreted by SNU-80 cells. Also when co-cultured with HB1.F3.CD and HB1.F3.CD.IFN-β cells, SNU-80 cell viability was reduced in presence of 5-FC. In this study, we proved the hNSCs expressing CD (HB1.F3.CD) and IFN-β (HB1.F3.CD.IFN-β) genes therapeutic effect. As a result, hNSC therapy with prodrug 5-FC may helpful for the treatment of human anaplastic thyroid cancer. Furthermore, we are currently studying on a xenograft in vivo model to prove that selective anti-tumor effect of hNSCs.