Anticancer effects of the engineered stem cells transduced with therapeutic genes via a selective tumor tropism caused by vascular endothelial growth factor toward HeLa cervical cancer cells

• Published in: Molecules and cells Vol. 36; no. 4; pp. 347 - 354
• Main Authors: Kim, H.S., Chungbuk National University, Cheongju, Republic of Korea, Yi, B.R., Chungbuk National University, Cheongju, Republic of Korea, Hwang, K.A., Chungbuk National University, Cheongju, Republic of Korea, Kim, S.U., Chung-Ang University College of Medicine, Seoul, Republic of Korea, Choi, K.C., Chungbuk National University, Cheongju, Republic of Korea
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.10.2013; Korean Society for Molecular and Cellular Biology; Korea Society for Molecular and Cellular Biology; 한국분자세포생물학회
• Subjects: Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cell Biology; Cell Line; Cell Movement; Cell Survival; Cervical cancer; cervical cancer, cytosine deaminase, GESTECs, interferon-beta, VEGF; Coculture Techniques; Cytosine Deaminase - genetics; Cytosine Deaminase - metabolism; Female; Fluorouracil - pharmacology; Genetic Engineering; Genetic Therapy; HeLa Cells; Humans; Interferon-beta - genetics; Interferon-beta - metabolism; Life Sciences; Research Article; Stem Cells - physiology; Transduction, Genetic; TROPISME; TROPISMO; TROPISMS; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - therapy; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor Receptor-2 - genetics; Vascular Endothelial Growth Factor Receptor-2 - metabolism; 생물학; cytosine deaminase; interferon-β; cervical cancer; VEGF; GESTECs
• ISSN: 1016-8478; 0219-1032
• DOI: 10.1007/s10059-013-0153-3

The aim of the present study was to investigate the therapeutic efficacy of genetically engineered stem cells (GESTECs) expressing bacterial cytosine deaminase (CD) and/ or human interferon-beta (IFN-β) gene against HeLa cervical cancer and the migration factors of the GESTECs toward the cancer cells. Anticancer effect of GESTECs was examined in a co-culture with HeLa cells using MTT assay to measure cell viability. A transwell migration assay was performed so as to assess the migration capability of the stem cells to cervical cancer cells. Next, several chemoattractant ligands and their receptors related to a selective migration of the stem cells toward HeLa cells were determined by real-time PCR. The cell viability of HeLa cells was decreased in response to 5-fluorocytosine (5-FC), a prodrug, indicating that 5-fluorouracil (5-FU), a toxic metabolite, was converted from 5-FC by CD gene and it caused the cell death in a co-culture system. When IFN-β was additionally expressed with CD gene by these GESTECs, the anticancer activity was significantly increased. In the migration assay, the GESTECs selectively migrated to HeLa cervical cancer cells. As results of real-time PCR, chemoattractant ligands such as MCP-1, SCF, and VEGF were expressed in HeLa cells, and several receptors such as uPAR, VEGFR2, and c-kit were produced by the GESTECs. These GESTECs transduced with CD gene and IFN- β may provide a potential of a novel gene therapy for anticervical cancer treatments via their selective tumor tropism derived from VEGF and VEGFR2 expressions between HeLa cells and the GESTECs.