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Dura promotes metastatic potential in prostate cancer through the CXCR2 pathway

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  • Published:
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Abstract

Purpose

Spinal metastases are common in cancer. This preferential migration/growth in the spine is not fully understood. Dura has been shown to affect the surrounding microenvironment and promote cancer growth. Here, we investigate the role of dural cytokines in promoting the metastatic potential of prostate cancer (PCa) and the involvement of the CXCR2 signaling pathway.

Methods

The role of dural conditioned media (DCM) in proliferation, migration and invasion of five PCa cell lines with various hormone sensitivities was assessed in the presence or absence of the CXCR2 inhibitor, SB225002. CXCR2 surface protein was examined by FACS. Cytokine levels were measured using a mouse cytokine array.

Results

We observed high levels of cytokines produced by dura and within the vertebral body bone marrow, namely CXCL1 and CXCL2, that act on the CXCR2 receptor. All prostate cell lines treated with DCM demonstrated significant increase in growth, migration and invasion regardless of androgen sensitivity, except PC3, which did not significantly increase in invasiveness. When treated with SB225002, the growth response to DCM by cells expressing the highest levels of CXCR2 as measured by FACS (LNCaP and 22Rv1) was blunted. The increase in migration was significantly decreased in all lines in the presence of SB225002. Interestingly, the invasion increase seen with DCM was unchanged when these cells were treated with the CXCR2 inhibitor, except PC3 did demonstrate a significant decrease in invasion.

Conclusion

DCM enhances the metastatic potential of PCa with increased proliferation, migration and invasion. This phenomenon is partly mediated through the CXCR2 pathway.

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Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

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Acknowledgements

The authors would like to thank Tom Cichonski for assistance with the preparation of this manuscript.

Funding

This work was supported in part by National Institutes of Health grant R21NS107879 (Alexandra Calinescu), P01CA093900 (R.T.), Rogel Cancer Center Grant G020989 (Alexandra Calinescu, N.J.S.), the Department of Defense Prostate Cancer Research Program PC170089 Early Investigator Award (N.J.S.), and VA Merit Review 1I01BX001370 (G.A.C.).

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Authors and Affiliations

  1. Department of Neurosurgery, University of Michigan, 3552 Taubman Center, 1500 E. Medical Center Dr., Ann Arbor, MI, 48109, USA

    Michael J. Strong, Sabrina Rocco & Nicholas J. Szerlip

  2. School of Dentistry, University of Alabama at Birmingham, Birmingham, AL, USA

    Russell Taichman

  3. Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA

    Gregory A. Clines

  4. Veterans Affairs Medical Center, Ann Arbor, MI, USA

    Gregory A. Clines & Nicholas J. Szerlip

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  1. Michael J. Strong
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Contributions

All authors contributed to the study conception and design. Material preparation and data collection and analysis were performed by MS, SR, RT, GC, and NS. The first draft of the manuscript was written by MS and NS, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Nicholas J. Szerlip.

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Strong, M.J., Rocco, S., Taichman, R. et al. Dura promotes metastatic potential in prostate cancer through the CXCR2 pathway. J Neurooncol 153, 33–42 (2021). https://doi.org/10.1007/s11060-021-03752-4

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