title: Irradiation enhances susceptibility of tumor cells to the antitumor effects of TNF-α activated adipose derived mesenchymal stem cells in breast cancer model.
abstract: Gene modified or cytokine activated mesenchymal stem cells (MSCs) have been used as a treatment in various types of cancer. Moreover, irradiation is usually applied as either a standard primary or adjuvant therapy. Here, we showed that the expression of TNF related apoptosis-inducing ligand (TRAIL) and Dickouf-3 (Dkk-3), the promising anticancer proteins, increased in murine adipose-derived mesenchymal stromal cells (AD-MSCs) following activation with TNF-α, resulting in the induction of apoptosis in cancer cells. Also, anticancer effects of TNF-α activated AD-MSCs were intensified with irradiation. In vivo results showed that TNF-α preactivated AD-MSCs combined with irradiation decreased tumor size and increased survival rate in tumor bearing mice. On the other hands, both TNF-α preactivated AD-MSCs with or without irradiation prevented metastasis in ling and liver, and increased apoptosis in tumor mass. Finally, flowcytometry assay demonstrated that naïve AD-MSCs combined with irradiation but not TNF-α activated MSCs with irradiation increased Treg population in lymph node and spleen. Altogether, obtained results suggest that TNF-α activated MSCs combined with irradiation therapy can serve as new strategy in breast cancer therapy.
authors.affiliation: Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.|Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Hemn
authors.initials: H
authors.lastname: Mohammadpour
authors.affiliation: Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Pourfathollah
authors.affiliation: Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
authors.forename: Mahin
authors.initials: M
authors.lastname: Nikougoftar Zarif
authors.affiliation: Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.
authors.forename: Amir Ali
authors.initials: AA
authors.lastname: Shahbazfar
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D011878:Radiotherapy / Q000379:methods*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C405061:Dkk3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha