TY - JOUR
T1 - The systemic administration of neural stem cells expressing an inducible and soluble form of growth arrest specific 1 inhibits mammary gland tumor growth and the formation of metastases
AU - Romero-Trejo, Daniel
AU - Mejía-Rodríguez, Rosalinda
AU - Sierra-Mondragón, Edith
AU - Navarrete, Araceli
AU - Pérez-Tapia, Mayra
AU - González, Rosa O.
AU - Segovia, José
N1 - Publisher Copyright:
© 2020 International Society for Cell & Gene Therapy
PY - 2021/3
Y1 - 2021/3
N2 - Background aims: Metastasis to different organs is the major cause of death in breast cancer patients. The poor clinical prognosis and lack of successful treatments for metastatic breast cancer patients demand the development of new tumor-selective therapies. Thus, it is necessary to develop treatments capable of releasing therapeutic agents to both primary tumors and metastases that avoid toxic side effects in normal tissue, and neural stem cells are an attractive vehicle for tracking tumor cells and delivering anti-cancer agents. The authorspreviously demonstrated that a soluble form of growth arrest specific 1 (GAS1) inhibits the growth of triple-negative breast tumors and glioblastoma. Methods: In this study, the authors engineered ReNcell CX (EMD Millipore, Temecula, CA, USA) neural progenitor cells to express truncated GAS1 (tGAS1) under a tetracycline/on inducible system using lentiviral vectors. Results: Here the authors show that treatment with ReNcell-tGAS1 in combination with tetracycline decreased primary tumor growth and inhibited the formation of metastases in tumor-bearing mice by diminishing the phosphorylation of AKT and ERK1/2 in orthotopic mammary gland tumors. Moreover, the authors observed that ReNcell-tGAS1 prolonged the survival of 4T1 tumor-bearing mice. Conclusions: These data suggest that the delivery of tGAS1 by ReNcell cells could be an effective adjuvant for the treatment of triple-negative breast cancer.
AB - Background aims: Metastasis to different organs is the major cause of death in breast cancer patients. The poor clinical prognosis and lack of successful treatments for metastatic breast cancer patients demand the development of new tumor-selective therapies. Thus, it is necessary to develop treatments capable of releasing therapeutic agents to both primary tumors and metastases that avoid toxic side effects in normal tissue, and neural stem cells are an attractive vehicle for tracking tumor cells and delivering anti-cancer agents. The authorspreviously demonstrated that a soluble form of growth arrest specific 1 (GAS1) inhibits the growth of triple-negative breast tumors and glioblastoma. Methods: In this study, the authors engineered ReNcell CX (EMD Millipore, Temecula, CA, USA) neural progenitor cells to express truncated GAS1 (tGAS1) under a tetracycline/on inducible system using lentiviral vectors. Results: Here the authors show that treatment with ReNcell-tGAS1 in combination with tetracycline decreased primary tumor growth and inhibited the formation of metastases in tumor-bearing mice by diminishing the phosphorylation of AKT and ERK1/2 in orthotopic mammary gland tumors. Moreover, the authors observed that ReNcell-tGAS1 prolonged the survival of 4T1 tumor-bearing mice. Conclusions: These data suggest that the delivery of tGAS1 by ReNcell cells could be an effective adjuvant for the treatment of triple-negative breast cancer.
KW - breast cancer
KW - gene therapy
KW - growth arrest specific 1
KW - metastases
KW - neural stem cells
UR - http://www.scopus.com/inward/record.url?scp=85095853588&partnerID=8YFLogxK
U2 - 10.1016/j.jcyt.2020.09.011
DO - 10.1016/j.jcyt.2020.09.011
M3 - Artículo
C2 - 33168454
AN - SCOPUS:85095853588
SN - 1465-3249
VL - 23
SP - 223
EP - 235
JO - Cytotherapy
JF - Cytotherapy
IS - 3
ER -