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Bone marrow mesenchymal stem cells promote the progression of prostate cancer through the SDF-1/CXCR4 axis in vivo and vitro

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Abstract

Purpose

The aim of this study was to investigate the involvement of the SDF-1/CXCR4 axis in the process of BMMSC homing in prostate cancer (PCa) in vivo and in vitro.

Methods

After verification of BMMSCs, we fixed the concentration gradient of SDF-1 for BMMSC cultivation to analyze CXCR4 expression by qRT-PCR and flow cytometric analysis. Furthermore, we developed a non-contact co-culture system and explored the participation of the SDF-1/CXCR4 axis in PCa using qRT-PCR, flow cytometry, and ELISA. In addition, A green fluorescent protein (GFP)-transplanted methylnitrosourea (MNU)-induced PCa mouse model was established to investigate the CXCR4 expression in vivo.

Results

The CXCR4 expression was up-regulated with the increase in SDF-1 concentrations, and elevated SDF-1 had a significant promoting effect on cell proliferation and migration in BMMSCs. Moreover, the CXCR4 expression of BMMSCs was significantly increased in the non-contact co-culture model with vascular endothelial cells (VECs), and analysis of this model also showed that the proliferation and migration of BMMSCs were promoted in the presence of VECs. The ELISA assay showed that the SDF-1 levels in the co-culture model at 48 h were significantly increased. Twenty of the GFP-transplanted mice were divided into a PCa group and a control group, and four GFP-transplanted mice were observed to have prostate tumorigenesis. It also showed that CXCR4 was obviously increased in the prostate tissue of PCa mice.

Conclusion

Our findings suggest that BMMSCs could home and promote the proliferation and migration of PCa through the SDF-1/CXCR4 axis in vivo and in vitro.

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Abbreviations

PCa:

Prostate cancer

PSA:

Prostate-specific antigen

RP:

Radical prostatectomy

ADT:

Androgen deprivation therapy

AR:

Androgen receptor

BMDCs:

Bone marrow-derived cells

BMMSCs:

Bone marrow mesenchymal stem cells

GFP:

Green fluorescent protein

TRAMP:

Transplanted transgenic adenocarcinoma of mouse prostate

MUN:

Methylnitrosourea

SDF-1:

Stromal cell-derived factor-1

VECs:

Vascular endothelial cells

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Funding

This study was supported by Tianjin Health Science and Technology Fund [No. KJ20051 and ZC20182] in collection, analysis, and interpretation of data as well as in writing the manuscript, and Tianjin Union Medical Center Fund [No. 2018YJZD004, 2020HL029, 2020YJ021] in the design of the study and collection, analysis, and interpretation of data.

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Authors and Affiliations

  1. The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, China

    F. Luo, Y. Su, Z. Zhang & J. Li

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  1. F. Luo
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  2. Y. Su
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  4. J. Li
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Corresponding author

Correspondence to J. Li.

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The authors declare that they have no competing interests.

Ethics approval

The present study was carried out at Tianjin Union Medical Center and was approved by the Institutional Ethics and Research Committee. The maximum tumor size that was permitted by the ethics committee in the experimental animals used was 15 mm, and we confirmed that the maximum tumor size was not exceeded 15 mm at any point during the duration of study.

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Supplementary Information

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12094_2021_2740_MOESM1_ESM.tif

Supplementary file1Supplement Fig. 1 A1: Experimental design picture about mouse model. C57BL/6 mice received lethal doses of 137Cs radiation to finish myeloablative, and subjected to retrobulbar injection with about 2 × 106 (100 μl) BMDCs from GFP transgenic mice. Chimera mice were performed an orthotopic injection of MNU (2 mg per mouse) every 3 weeks to induce prostate cancer. A2: Schematic diagram of non-contact model of BMMSCs and VECs cells. B1-4: The separation superstition of BM-MSCS in GFP transgenic mice. C1: Collection of Blood sample of Chimera mice from inner canthus. C2: Castration surgery of Chimera mice. C3-4: MNU injection into mouse prostate (TIF 7160 KB)

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Luo, F., Su, Y., Zhang, Z. et al. Bone marrow mesenchymal stem cells promote the progression of prostate cancer through the SDF-1/CXCR4 axis in vivo and vitro. Clin Transl Oncol 24, 892–901 (2022). https://doi.org/10.1007/s12094-021-02740-4

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