A Potential Therapy Using Engineered Stem Cells Prevented Malignant Melanoma in Cellular and Xenograft Mouse Models
- Author:
Jae Rim HEO
1
;
Kyung A HWANG
;
Seung U KIM
;
Kyung Chul CHOI
Author Information
- Publication Type:Original Article
- Keywords: Melanoma; Human neural stem cells; Flucytosine; Cytosine deaminase; Human interferon-β
- MeSH: Animals; Cell Line; Cytosine Deaminase; Epithelial-Mesenchymal Transition; Flucytosine; Fluorouracil; Heterografts; Humans; In Vitro Techniques; Melanoma; Mental Competency; Mice; Neoplasm Metastasis; Neural Stem Cells; Stem Cells
- From:Cancer Research and Treatment 2019;51(2):797-811
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: In the present study, human neural stem cells (hNSCs) with tumor-tropic behavior were used as drug delivery vehicle to selectively target melanoma. A hNSC line (HB1.F3) was transduced into two types: one expressed only the cytosine deaminase (CD) gene (HB1.F3. CD) and the other expressed both CD and human interferon-β (IFN-β) genes (HB1.F3.CD. IFN-β). MATERIALS AND METHODS: This study verified the tumor-tropic migratory competence of engineered hNSCs on melanoma (A375SM) using a modified Boyden chamber assay in vitro and CM-DiI staining in vivo. The antitumor effect of HB1.F3.CD and HB1.F3.CD.IFN-β on melanoma was also confirmed using an MTT assay in vitro and xenograft mouse models. RESULTS: A secreted form of IFN-β from the HB1.F3.CD.IFN-β cells modified the epithelial-mesenchymal transition (EMT) process and metastasis of melanoma. 5-Fluorouracil treatment also accelerated the expression of the pro-apoptotic protein BAX and decelerated the expression of the anti-apoptotic protein Bcl-xL on melanoma cell line. CONCLUSION: Our results illustrate that engineered hNSCs prevented malignant melanoma cells from proliferating in the presence of the prodrug, and the form that secreted IFN-β intervened in the EMT process and melanoma metastasis. Hence, neural stem cell-directed enzyme/prodrug therapy is a plausible treatment for malignant melanoma.
