Author/Authors :
Pourbagher, Roghayeh 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 , Ghorbani, Hossein Department of Pathology - Rohani Hospital - Babol University of Medical Sciences, Babol, Iran , Akhavan-Niaki, Haleh Cellular and Molecular Biology Research Center - Health Research Institute - Babol University of Medical Sciences, Babol, Iran , Jorsaraei, Gholam Ali Fatemeh Zahra Infertility and Reproductive Health Research Centre - Health Research Institute - Babol University of Medical Sciences, Babol, Iran , Fattahi, Sadegh Cellular and Molecular Biology Research Center - Health Research Institute - Babol University of Medical Sciences, Babol, Iran , Ghooran, Sahar Department of Pathology - Rohani Hospital - Babol University of Medical Sciences, Babol, Iran , Abedian, Zeinab Dental Materials Research Center - Dental Faculty - Babol University of Medical Sciences, Babol, Iran , Ghasemi, Masoumeh Cellular and Molecular Biology Research Center - Health Research Institute - Babol University of Medical Sciences, Babol, Iran , Saeedi, Fatemeh 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 , Jafari, Negar 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 , Kalali, Behnam Institute for Medical Microbiology - Immunology and Hygiene - Technische Universität München - Munich, Germany , Mostafazadeh, Amrollah Cellular and Molecular Biology Research Center - Health Research Institute - Babol University of Medical Sciences, Babol, Iran
Abstract :
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.
