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en Downregulation of Stemness Genes and Induction of Necrosis in Rat LA7 Cancer Stem Cells Induced Tumors Treated with Starved Fibroblasts Culture Supernatant زیست شناسی ملکولی Molecular Biology مقالات اصلی Original Article <div style="text-align: justify;">Background: Stem cell differentiation therapy is a promising strategy in cancer treatment. we show that protein cocktail prepared from serum starved fibroblasts has therapeutic potential based on this strategy. Methods: The condition medium was prepared from foreskin isolated fibroblasts and analyzed by Liquid chromatography electrospray ionization mass spectrometry-mass spectrometry (LC-ESI-MS/MS). LA7 mammary gland cancer stem cells originated tumors were induced in Sprague Dawley rats. The rats treated subcutaneously with DMEM (group A), condition medium (group B), or normal saline (group C) once daily for 7 days. Then the tumors were removed and divided into the two parts, one part was used to quantify gene expression by stem-loop RT-qPCR assay and the other part was used for Hematoxylin & Eosin (H & E), Giemsa, and immunohistochemistry (IHC) staining. Results: All induced tumors appeared as sarcomatoid carcinoma (SC). Immunohistochemistry staining confirmed this conclusion by recognizing the tumor as Ki67+, cytokeratin+, vimentine+, and estrogen receptor negative SC. RT-qPCR analysis revealed that Oct4-, Sox-2, Nanog- gene expression was much reduced in the condition medium treated tumors versus proper controls (p< 0.05). Tissue necrosis was more prevalent in this group while tumors volume was diminished almost by 40%. The LC-ESI-MS/MS analysis unrevealed the stemness reducing and the cell death inducing proteins such as, pigment epithelium-derived factor (PEDF), insulin like growth factor binding protein-5 (IGFBP-5) and -7 (IGFBP-7) in the condition medium. Conclusions: This study showed that the substances released from starved human fibroblasts were able to down-regulate the stemness-related genes and induce necrosis in LA7 derived tumors.</div> Breast cancer, Cancer Stem cells, Cell differentiation, Fibroblasts, Gene expression. 105 118 http://rbmb.net/browse.php?a_code=A-10-595-1&slc_lang=en&sid=1 Roghayeh Pourbagher 100319475328460012765 100319475328460012765 No Student Research Committee, Babol University of Medical Sciences, Babol, Iran & Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran. Hossein Ghorbani 100319475328460012766 100319475328460012766 No Department of Pathology, Rohani Hospital, Babol University of Medical Sciences, Babol, Iran. Haleh Akhavan-Niaki 100319475328460012767 100319475328460012767 No Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran. Seyed Gholam Ali Jorsaraei 100319475328460012768 100319475328460012768 No Fatemeh Zahra Infertility and Reproductive Health Research Centre, Health Research Institute, Babol University of Medical Sciences, Babol, Iran. Sadegh Fattahi 100319475328460012769 100319475328460012769 No Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran. Sahar Ghooran 100319475328460012770 100319475328460012770 No Department of Pathology, Rohani Hospital, Babol University of Medical Sciences, Babol, Iran. Zeinab Abedian 100319475328460012771 100319475328460012771 No Student Research Committee, Babol University of Medical Sciences, Babol, Iran & Dental Materials Research Center, Dental Faculty, Babol University of Medical Sciences, Babol, Iran. Masoumeh Ghasemi 100319475328460012772 100319475328460012772 No Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran. Fatemeh Saeedi 100319475328460012773 100319475328460012773 No Student Research Committee, Babol University of Medical Sciences, Babol, Iran & Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran. Negar Jafari 100319475328460012774 100319475328460012774 No Student Research Committee, Babol University of Medical Sciences, Babol, Iran & Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran. Behnam Kalali 100319475328460012775 100319475328460012775 No Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany. Amrollah Mostafazadeh 100319475328460012776 100319475328460012776 Yes Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.