Sara Zahedi1, Karim Shamsasenjan1, Aliakbar Movassaghpour1, Parvin Akbarzadehlaleh2. 1. Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 2. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Abstract
Purpose: Mesenchymal Stem Cells (MSCs) are one of the essential members of Bone Marrow (BM) microenvironment and the cells affect normal and malignant cells in BM milieu. One of the most important hematological malignancies is Multiple Myeloma (MM). Numerous studies reported various effects of MSCs on myeloma cells. MSCs initiate various signaling pathways in myeloma cells, particularly NF-kβ. NF-kβ signaling pathway plays pivotal role in the survival, proliferation and resistance of myeloma cells to the anticancer drugs, therefore this pathway can be said to be a vital target for cancer therapy. This study examined the relationship between U266 cells and MSCs. Methods: U266 cells were cultured with Umbilical Cord Blood derived-MSCs (UCB-MSCs) and Conditioned Medium (C.M). Effect of UCB-MSCs and C.M on proliferation rate and CD54 expression of U266 cells were examined with MTT assay and Flowcytometry respectively. Furthermore, expression of CXCL1, PECAM-1, JUNB, CCL2, CD44, CCL4, IL-6, and IL-8 were analyzed by Real Time-PCR (RT-PCR). Moreover, status of p65 protein in NF-kβ pathway assessed by western blotting. Results: Our findings confirm that UCB-MSCs support U266 cells proliferation and they increase CD54 expression. In addition, we demonstrate that UCB-MSCs alter the expression of CCL4, IL-6, IL-8, CXCL1 and the levels of phosphorylated p65 in U266 cells. Conclusion: Our study provides a novel sight to the role of MSCs in the activation of NF-kβ signaling pathway. So, NF-kβ signaling pathway will be targeted in future therapies against MM.
Purpose: Mesenchymal Stem Cells (MSCs) are one of the essential members of Bone Marrow (BM) microenvironment and the cells affect normal and malignant cells in BM milieu. One of the most important hematological malignancies is Multiple Myeloma (MM). Numerous studies reported various effects of MSCs on myeloma cells. MSCs initiate various signaling pathways in myeloma cells, particularly NF-kβ. NF-kβ signaling pathway plays pivotal role in the survival, proliferation and resistance of myeloma cells to the anticancer drugs, therefore this pathway can be said to be a vital target for cancer therapy. This study examined the relationship between U266 cells and MSCs. Methods: U266 cells were cultured with Umbilical Cord Blood derived-MSCs (UCB-MSCs) and Conditioned Medium (C.M). Effect of UCB-MSCs and C.M on proliferation rate and CD54 expression of U266 cells were examined with MTT assay and Flowcytometry respectively. Furthermore, expression of CXCL1, PECAM-1, JUNB, CCL2, CD44, CCL4, IL-6, and IL-8 were analyzed by Real Time-PCR (RT-PCR). Moreover, status of p65 protein in NF-kβ pathway assessed by western blotting. Results: Our findings confirm that UCB-MSCs support U266 cells proliferation and they increase CD54 expression. In addition, we demonstrate that UCB-MSCs alter the expression of CCL4, IL-6, IL-8, CXCL1 and the levels of phosphorylated p65 in U266 cells. Conclusion: Our study provides a novel sight to the role of MSCs in the activation of NF-kβ signaling pathway. So, NF-kβ signaling pathway will be targeted in future therapies against MM.
Authors: F Merico; L Bergui; M G Gregoretti; P Ghia; G Aimo; I J Lindley; F Caligaris-Cappio Journal: Clin Exp Immunol Date: 1993-04 Impact factor: 4.330
Authors: Ulrike Heider; Claudia Fleissner; Ivana Zavrski; Martin Kaiser; Monica Hecht; Christian Jakob; Orhan Sezer Journal: Eur J Cancer Date: 2006-06-09 Impact factor: 9.162
Authors: C S Debes-Marun; G W Dewald; S Bryant; E Picken; R Santana-Dávila; N González-Paz; J M Winkler; R A Kyle; M A Gertz; T E Witzig; A Dispenzieri; M Q Lacy; S V Rajkumar; J A Lust; P R Greipp; R Fonseca Journal: Leukemia Date: 2003-02 Impact factor: 11.528