Koushan Sineh Sepehr1, Alireza Razavi2, Zuhair Mohammad Hassan3, Abdolreza Fazel4, Meghdad Abdollahpour-Alitappeh5, Majid Mossahebi-Mohammadi6, Mir Saeed Yekaninejad7, Behrouz Farhadihosseinabadi8, Seyed Mahmoud Hashemi9,10,11. 1. Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran. 2. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. razavial@tums.ac.ir. 3. Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. 4. Cancer Research Center, Golestan University of Medical Sciences, Gorgan, Iran. 5. Cellular and Molecular Biology Research Center, Larestan University of Medical Sciences, Larestan, Iran. 6. Sarem Cell Research Center(SCRC), Sarem Women's Hospital, Tehran, Iran. 7. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. 8. Neuroscience Research Center (NRC), Iran University of Medical Sciences, Tehran, Iran. 9. Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. smmhashemi@sbmu.ac.ir. 10. Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. smmhashemi@sbmu.ac.ir. 11. Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. smmhashemi@sbmu.ac.ir.
Abstract
OBJECTIVE: Mesenchymal stem cells (MSCs), one of the most important stromal cells in the tumor microenvironment, play a major role in the immunomodulation and development of tumors. In contrast to immunomodulatory effects of bone marrow-derived MSCs, resident MSCs were not well studied in tumor. The aim of this study was to compare the immunomodulatory properties and protein secretion profiles of MSCs isolated from breast tumor (T-MSC) and normal breast adipose tissue (N-MSC). MATERIALS AND METHODS: T-MSCs and N-MSCs were isolated by the explant culture method and characterized, and their immunomodulatory function was assessed on peripheral blood lymphocytes (PBLs) by evaluating the effects of MSC conditioned media on the proliferation and induction of some cytokines and regulatory T cells (Tregs) by BrdU assay, ELISA, and flow cytometry. In addition, we compared the secretion of indoleamine 2,3-dioxygenase (IDO), vascular endothelial growth factor (VEGF), matrix metallopeptidase (MMP)-2, MMP-9, and Galectin-1. RESULTS: T-MSCs showed a higher secretion of transforming growth factor beta (TGF-β), prostaglandin E2 (PGE2), IDO, and VEGF and lower secretion of MMP-2 and MMP-9 compared with N-MSCs. However, no significant difference was found in the secretion of interferon gamma (IFN-γ), interleukin 10 (IL10), IL4, IL17, and Galectin-1 in T-MSCs and N-MSCs. The immunomodulatory effect of soluble factors on PBLs showed that T-MSCs, in contrast to N-MSCs, stimulate PBL proliferation. Importantly, the ability of T-MSCs to induce IL10, TGF-β, IFN-γ, and PGE2 was higher than that of N-MSCs. In addition, T-MSCs and N-MSCs exhibited no significant difference in Treg induction. CONCLUSION: MSCs educated in stage II breast cancer and normal breast adipose tissue, although sharing a similar morphology and immunophenotype, exhibited a clearly different profile in some immunomodulatory functions and protein secretions.
OBJECTIVE: Mesenchymal stem cells (MSCs), one of the most important stromal cells in the tumor microenvironment, play a major role in the immunomodulation and development of tumors. In contrast to immunomodulatory effects of bone marrow-derived MSCs, resident MSCs were not well studied in tumor. The aim of this study was to compare the immunomodulatory properties and protein secretion profiles of MSCs isolated from breast tumor (T-MSC) and normal breast adipose tissue (N-MSC). MATERIALS AND METHODS: T-MSCs and N-MSCs were isolated by the explant culture method and characterized, and their immunomodulatory function was assessed on peripheral blood lymphocytes (PBLs) by evaluating the effects of MSC conditioned media on the proliferation and induction of some cytokines and regulatory T cells (Tregs) by BrdU assay, ELISA, and flow cytometry. In addition, we compared the secretion of indoleamine 2,3-dioxygenase (IDO), vascular endothelial growth factor (VEGF), matrix metallopeptidase (MMP)-2, MMP-9, and Galectin-1. RESULTS: T-MSCs showed a higher secretion of transforming growth factor beta (TGF-β), prostaglandin E2 (PGE2), IDO, and VEGF and lower secretion of MMP-2 and MMP-9 compared with N-MSCs. However, no significant difference was found in the secretion of interferon gamma (IFN-γ), interleukin 10 (IL10), IL4, IL17, and Galectin-1 in T-MSCs and N-MSCs. The immunomodulatory effect of soluble factors on PBLs showed that T-MSCs, in contrast to N-MSCs, stimulate PBL proliferation. Importantly, the ability of T-MSCs to induce IL10, TGF-β, IFN-γ, and PGE2 was higher than that of N-MSCs. In addition, T-MSCs and N-MSCs exhibited no significant difference in Treg induction. CONCLUSION: MSCs educated in stage II breast cancer and normal breast adipose tissue, although sharing a similar morphology and immunophenotype, exhibited a clearly different profile in some immunomodulatory functions and protein secretions.
Entities:
Keywords:
Breast cancer; Immunomodulatory; Mesenchymal stem cells (MSCs)