SRC3 expressed in BMSCs promotes growth and migration of multiple myeloma cells by regulating the expression of Cx43

Jin,Jie; Wang,Tao; Wang,Yu; Chen,Shidi; Li,Zheng; Li,Xiang; Zhang,Jiazhen; Wang,Jin

doi:10.3892/ijo.2017.4171

SRC3 expressed in BMSCs promotes growth and migration of multiple myeloma cells by regulating the expression of Cx43

Authors:
- Jie Jin
- Tao Wang
- Yu Wang
- Shidi Chen
- Zheng Li
- Xiang Li
- Jiazhen Zhang
- Jin Wang
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Affiliations: Department of Hematology, The Third Affiliated Daping Hospital of Army Medical University, Chongqing 400042, P.R. China, Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, College of Preventive Medicine, Army Medical University, Chongqing 400038, P.R. China
Published online on: October 20, 2017 https://doi.org/10.3892/ijo.2017.4171
Pages: 1694-1704
Copyright: © Jin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Interactions between bone marrow stromal cells (BMSCs) and multiple myeloma cells significantly contribute to the progression of multiple myeloma (MM). However, little is known about the molecular mechanisms that regulate these interactions. Connexin-43 (Cx-43) has been implicated in the interplay between BMSCs and MM cells. In this study, we hypothesized that the steroid receptor co-activator-3 (SRC3) expressed in BMSCs regulates the expression of Cx-43 to promote the proliferation and migration of myeloma cells. To address this, we co-cultured a human multiple myeloma cell line, RPMI-8226 transfected with either control BMSCs or sh-SRC3-BMSCs. We found that knocking down SRC3 expression in BMSCs inhibited the proliferation and migration of RPMI-8226 cells. In addition, we found that co-culturing RPMI 8266 cells with BMSCs increased Cx43 expression, while knocking down SRC3 expression in BMSCs decreased Cx43 expression. Moreover, our work revealed that SRC3 in BMSCs regulates Cx43 expression via the mitogen-activated protein kinase (MAPK) pathway. To validate this result in vivo, we knocked down SRC3 expression in BMSCs in nude mice and found that tumor growth and cell apoptosis were significantly decreased. In addition, mice treated with either RPMI 8266 cells overexpressing Cx43 or with a P38 MAPK inhibitor (SB202190) exhibited increased intratumoral leukocyte populations and promoted cell apoptosis in tumor tissue. Our findings demonstrate how SRC3 and Cx43 regulation between BMSCs and myeloma cells mediate cell growth and disease progression, with potential implications for prognosis and therapeutic interventions.

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