Michael J Strong1, Sabrina Rocco1, Russell Taichman2, Gregory A Clines3,4, Nicholas J Szerlip5,6. 1. Department of Neurosurgery, University of Michigan, 3552 Taubman Center, 1500 E. Medical Center Dr., Ann Arbor, MI, 48109, USA. 2. School of Dentistry, University of Alabama at Birmingham, Birmingham, AL, USA. 3. Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. 4. Veterans Affairs Medical Center, Ann Arbor, MI, USA. 5. Department of Neurosurgery, University of Michigan, 3552 Taubman Center, 1500 E. Medical Center Dr., Ann Arbor, MI, 48109, USA. nszerlip@med.umich.edu. 6. Veterans Affairs Medical Center, Ann Arbor, MI, USA. nszerlip@med.umich.edu.
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.
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.
Authors: Daniel M Sciubba; Rory J Petteys; Mark B Dekutoski; Charles G Fisher; Michael G Fehlings; Stephen L Ondra; Laurence D Rhines; Ziya L Gokaslan Journal: J Neurosurg Spine Date: 2010-07
Authors: Jason A Spector; Joshua A Greenwald; Stephen M Warren; Pierre J Bouletreau; Robert C Detch; Peter J Fagenholz; Francesca E Crisera; Michael T Longaker Journal: Plast Reconstr Surg Date: 2002-02 Impact factor: 4.730
Authors: Marissa Guo; Kristen L Kolberg; Eleanor C Smith; Brandon W Smith; Jonah E Yousif; Jason L Kessler; Joseph R Linzey; Anda-Alexandra Calinescu; Gregory A Clines; Daniel E Spratt; Nicholas J Szerlip Journal: World Neurosurg Date: 2018-08-13 Impact factor: 2.104
Authors: J K Simmons; B E Hildreth; W Supsavhad; S M Elshafae; B B Hassan; W P Dirksen; R E Toribio; T J Rosol Journal: Vet Pathol Date: 2015-05-28 Impact factor: 2.221
Authors: M M Muresan; P Olivier; J Leclère; F Sirveaux; L Brunaud; M Klein; R Zarnegar; G Weryha Journal: Endocr Relat Cancer Date: 2008-03 Impact factor: 5.678
Authors: Michael J Strong; Sravanthi Koduri; Jodi A Allison; Cecilia M Pesavento; Sebele Ogunsola; Oludotun Ogunsola; Timothy J Yee; Siri Sahib S Khalsa; Yamaan S Saadeh; Jacob R Joseph; Osama N Kashlan; Paul Park; Mark E Oppenlander; Nicholas J Szerlip Journal: J Neurooncol Date: 2022-05-17 Impact factor: 4.130
Authors: Aqila A Ahmed; Michael J Strong; Xiaofeng Zhou; Tyler Robinson; Sabrina Rocco; Geoffrey W Siegel; Gregory A Clines; Bethany B Moore; Evan T Keller; Nicholas J Szerlip Journal: PLoS One Date: 2022-04-27 Impact factor: 3.752