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 |
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| Authors: | Daniel Romero-Trejo Rosalinda Mejía-Rodríguez Edith Sierra-Mondragón Araceli Navarrete Mayra Pérez-Tapia Rosa O González José Segovia |
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| Affiliation: | 1. Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, México;2. Departamento de Inmunología Escuela Nacional de Ciencias Biológicas, del Instituto Politécnico Nacional, México;3. Departamento de Matemáticas, Universidad Autónoma Metropolitana-Iztapalapa (UAM-I), México;1. Biomedical Ethics Research Program, Mayo Clinic, Rochester, Minnesota, USA;2. University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA;3. Department of Biological Sciences, College of Science, University of Notre Dame, Notre Dame, Indiana, USA;4. Department of Anatomy and Neuroscience, Centre for Stem Cell Systems, University of Melbourne, Parkville, Australia;5. Division of Pulmonary and Critical Care Medicine and Biomedical Ethics Research Program, Mayo Clinic, Rochester, Minnesota, USA;6. Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA;7. Department of Orthopedic Surgery and Center for Regenerative Medicine, Mayo Clinic College of Medicine, Jacksonville, Florida, USA;8. Biomedical Ethics Research Program and Center for Regenerative Medicine, Mayo Clinic, Rochester, Minnesota, USA;1. Center for Autoimmune Genomics and Etiology, Cincinnati Children''s Hospital Medical Center, Cincinnati, Ohio, USA;2. Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA;3. Immunology Graduate Training Program, Cincinnati, Ohio, USA;4. Molecular and Developmental Biology Graduate Program, Cincinnati, Ohio, USA;5. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA;6. Division of Rheumatology, Cincinnati Children''s Hospital Medical Center, Cincinnati, Ohio, USA;1. Seattle Children''s Research Institute, Seattle, Washington, USA;2. University of California San Francisco, San Francisco, California, USA;3. Children''s Hospital Los Angeles, Los Angeles, California, USA;4. Center for Cancer and Immunology Research, Center for Cancer and Blood Disorders, Children''s National Hospital, Washington, DC, USA;5. The George Washington University, Washington, DC, USA;1. Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China;2. Tianjin General Surgery Institute, Tianjin, China;1. Government Hospital, Velayuthampalayam, Karur, Tamil Nadu, India;2. Orthopaedic Research Group, Coimbatore, Tamil Nadu, India;3. Indian Stem Cells Study Group, Lucknow, India;4. Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, India;5. Department of Orthopaedics, Kalpana Chawla Government Medical College & Hospital, Karnal, India;1. Department of Molecular Biology and Gene Therapy, Global Biotherapeutics (GBT), Mexico City, Mexico;2. Faculty of Chemical and Biological Sciences, Autonomous University of Campeche, Campeche, Mexico |
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| Abstract: | Background aimsMetastasis 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.MethodsIn 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.ResultsHere 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.ConclusionsThese data suggest that the delivery of tGAS1 by ReNcell cells could be an effective adjuvant for the treatment of triple-negative breast cancer. |
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