Bone marrow mesenchymal stem cells participate in prostate carcinogenesis and promote growth of prostate cancer by cell fusion in vivo
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Fei Luo1,2,*, Tong Liu1,*, Jianan Wang1, Jian Li2, Pengde Ma1, Hao Ding1, Guowei Feng3, Dong Lin4, Yong Xu1, Kuo Yang1
1Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin, China
2Department of Urology, Tianjin Union Medical Center, Tianjin, China
3Department of Genitourinary Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
4BC Cancer Research Centre, Vancouver, Canada
*These authors contributed equally to this work
Kuo Yang, email: [email protected]
Yong Xu, email: [email protected]
Keywords: bone marrow transplantation, prostate cancer, tumorigenesis, bone marrow-derived mesenchymal stem cells
Received: October 14, 2015 Accepted: April 08, 2016 Published: April 27, 2016
The tumor microenvironment is comprised of diverse stromal cells that contribute towards tumor progression. As a result, there has been a growing interest in the role of bone marrow derived cells (BMDCs) in cancer progression. However, the role of BMDCs in prostate cancer (PCa) progression still remains unclear. In this study, we established GFP bone marrow transplanted TRAMP and MUN-induced prostate cancer models, in order to investigate the role of BMDCs in prostate cancer progression. By tracing GFP positive cells, we observed that BMDCS were recruited into mouse prostate tissues during tumorigenesis. GFP+/Sca-1+/CD45− BMDCs were significantly increased in the MNU-induced PCa group, as compared to the citrated-treated control group (2.67 ± 0.25% vs 0.67 ± 0.31%, p = 0.006). However, there were no significant differences found in GFP+/Sca-1+/CD45+ cell populations between the two groups (0.27 ± 0.15% vs 0.10 ± 0.10%, p = 0.334). Moreover, co-grafting of bone marrow mesenchymal stem cells (BMMSCs) and RM1 cells were found to promote RM1 tumor growth in vivo, and cell fusion was observed in RM-1+BMMSCs xenografts. Therefore, the data suggests that BMDCs can be recruited to the prostate during carcinogenesis, and that BMMSCs may promote the growth of PCa.
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