Parasites, Hosts and Diseases

The Korea Society for Parasitology and Tropical Medicine (대한기생충학·열대의학회)
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Involvement of Macrophages in Proliferation of Prostate Cancer Cells Infected with Trichomonas vaginalis

  • Kim, Kyu-Shik (Department of Urology, Hanyang University Guri Hospital, Hanyang University College of Medicine) ;
  • Moon, Hong-Sang (Department of Urology, Hanyang University Guri Hospital, Hanyang University College of Medicine) ;
  • Kim, Sang-Su (Department of Environmental Biology and Medical Parasitology, Hanyang University College of Medicine) ;
  • Ryu, Jae-Sook (Department of Environmental Biology and Medical Parasitology, Hanyang University College of Medicine)
  • Received : 2021.09.24
  • Accepted : 2021.11.18
  • Published : 2021.12.31
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Abstract

Macrophages play a key role in chronic inflammation, and are the most abundant immune cells in the tumor microenvironment. We investigated whether an interaction between inflamed prostate cancer cells stimulated with Trichomonas vaginalis and macrophages stimulates the proliferation of the cancer cells. Conditioned medium was prepared from T. vaginalis-infected (TCM) and uninfected (CM) mouse prostate cancer (PCa) cell line (TRAMP-C2 cells). Thereafter conditioned medium was prepared from macrophages (J774A.1 cell line) after incubation with CM (MCM) or TCM (MTCM). When TRAMP-C2 cells were stimulated with T. vaginalis, protein and mRNA levels of CXCL1 and CCL2 increased, and migration of macrophages toward TCM was more extensive than towards CM. Macrophages stimulated with TCM produced higher levels of CCL2, IL-6, TNF-α, their mRNAs than macrophages stimulated with CM. MTCM stimulated the proliferation and invasiveness of TRAMP-C2 cells as well as the expression of cytokine receptors (CCR2, GP130, CXCR2). Importantly, blocking of each cytokine receptors with anti-cytokine receptor antibody significantly reduced the proliferation and invasiveness of TRAMP-C2 cells. We conclude that inflammatory mediators released by TRAMP-C2 cells in response to infection by T. vaginalis stimulate the migration and activation of macrophages and the activated macrophages stimulate the proliferation and invasiveness of the TRAMP-C2 cells via cytokine-cytokine receptor binding. Our results therefore suggested that macrophages contribute to the exacerbation of PCa due to inflammation of prostate cancer cells reacted with T. vaginalis.

Keywords

Acknowledgement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Conrad MD, Gorman AW, Schillinger JA, Fiori PL, Arroyo R, Malla N, Dubey ML, Gonzalez J, Blank S, Secor WE, Carlton JM. Extensive genetic diversity, unique population structure and evidence of genetic exchange in the sexually transmitted parasite Trichomonas vaginalis. PLoS Negl Trop Dis 2012; 6: e1573. https://doi.org/10.1371/journal.pntd.0001573
  2. Chetty R, Mabaso N, Abbai N. Genotypic variation in Trichomonas vaginalis detected in South African pregnant women. Infect Dis Obstet Gynecol 2020; 2020: 1687427. https://doi.org/10.1155/2020/1687427
  3. Abdolrasouli A, Amin A, Baharsefat M, Roushan A, Mofidi S. Persistent urethritis and prostatitis due to Trichomonas vaginalis: a case report. Can J Infect Dis Med Microbiol 2007; 18: 308-310. https://doi.org/10.1155/2007/196046
  4. Sutcliffe S, Neace C, Magnuson NS, Reeves R, Alderete JF. Trichomonosis, a common curable STI, and prostate carcinogenesis - a proposed molecular mechanism. PLoS Pathog 2012; 8: e1002801. https://doi.org/10.1371/journal.ppat.1002801
  5. Gardner WA Jr, Culberson DE, Bennett BD. Trichomonas vaginalis in the prostate gland. Arch Pathol Lab Med 1986; 110: 430-432.
  6. Kim JH, Moon HS, Kim KS, Hwang HS, Ryu JS, Park SY. Comparison of seropositivity to Trichomonas vaginalis between men with prostatic tumor and normal men. Korean J Parasitol 2019; 57: 21-25. http://doi.org/10.3347/kjp.2019.57.1.21
  7. Adekoya TO, Richardson RM. Cytokines and chemokines as mediators of prostate cancer metastasis. Int J Mol Sci 2020; 21: 4449. http://doi.org/10.3390/ijms21124449
  8. Kim SS, Kim KS, Han IH, Kim Y, Bang SS, Kim JH, Kim YS, Choi SY, Ryu JS. Proliferation of mouse prostate cancer cells inflamed by Trichomonas vaginalis. Korean J Parasitol 2021; 59: 547-556. http://doi.org/10.3347/kjp.2021.59.6.547
  9. Schoppmann SF, Birner P, Stockl J, Kalt R, Ullrich R, Caucig C, Kriehuber E, Nagy K, Alitalo K, Kerjaschki D. Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis. Am J Pathol 2002; 161: 947-956. http://doi.org/10.1016/S0002-9440(10)64255-1
  10. Lissbrant IF, Stattin P, Wikstrom P, Damber JE, Egevad L, Bergh A. Tumor associated macrophages in human prostate cancer: relation to clinicopathological variables and survival. Int J Oncol 2000; 17: 445-451. http://doi.org/10.3892/ijo.17.3.445
  11. Chung HY, Kim JH, Han IH, Ryu JS. Polarization of M2 macrophages by interaction between prostate cancer cells treated with Trichomonas vaginalis and adipocytes. Korean J Parasitol 2020; 58: 217-227. http://doi.org/10.3347/kjp.2020.58.3.217
  12. Kim JH, Han IH, Shin SJ, Park SY, Chung HY, Ryu JS. Signaling role of adipocyte leptin in prostate cell proliferation induced by Trichomonas vaginalis. Korean J Parasitol 2021; 59: 235-249. http://doi.org/10.3347/kjp.2021.59.3.235
  13. Han IH, Song HO, Ryu JS. IL-6 produced by prostate epithelial cells stimulated with Trichomonas vaginalis promotes proliferation of prostate cancer cells by inducing M2 polarization of THP-1-derived macrophages. PLoS Negl Trop Dis 2020; 14: e0008126. http://doi.org/10.1371/journal.pntd.0008126
  14. Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol 2005; 5: 953-964. http://www.doi.org/10.1038/nri1733
  15. Ginhoux F, Guilliams M. Tissue-resident macrophage ontogeny and homeostasis. Immunity 2016; 44: 439-449. http://www.doi.org/10.1016/j.immuni.2016.02.024
  16. Locati M, Curtale G, Alberto Mantovani A. Diversity, mechanisms and significance of macrophage plasticity. Annu Rev Pathol 2020; 15: 123-147. http://www.doi.org/10.1146/annurevpathmechdis-012418-012718
  17. Mantovani A, Marchesi F, Malesci A, Laghi L, Allavena P. Tumorassociated macrophages as treatment targets in oncology. Nat Rev Clin Oncol 2017; 14: 399-416. http://www.doi.org/10.1038/nrclinonc.2016.217
  18. Noy R, Pollard JW. Tumor-associated macrophages: from mechanisms to therapy. Immunity 2014; 41:49-61. http://doi: 10.1016/j.immuni.2014.06.010.
  19. Dranoff G. Cytokines in cancer pathogenesis and cancer therapy. Nat Rev Cancer 2004; 4: 11-22. http://www.doi.org/10.1038/nrc1252
  20. Chow MT, Luster AD. Chemokines in cancer. Cancer Immunol Res 2014; 2: 1125-1131. http://doi: 10.1158/2326-6066.CIR-14-0160.
  21. Nagarsheth N, Wicha MS, Zou W. Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nat Rev Immunol 2017; 17: 559-572. http://www.doi.org/10.1038/nri.2017.49
  22. Lu Y, Cai Z, Galson DL, Xiao G, Liu Y, George DE, Melhem MF, Yao Z, Zhang J. Monocyte chemotactic protein-1 (MCP-1) acts as a paracrine and autocrine factor for prostate cancer growth and invasion. Prostate 2006; 66: 1311-1318. http://www.doi.org/10.1002/pros.20464
  23. Lu Y, Chen Q, Corey E, Xie W, Fan J, Mizokami A, Zhang J. Activation of MCP-1/CCR2 axis promotes prostate cancer growth in bone. Clin Exp Metastasis 2009; 26: 161-169. http://www.doi.org/10.1007/s10585-008-9226-7
  24. Loberg RD, Day LL, Harwood J, Ying C, St John LN, Giles R, Neeley CK, Pienta KJ. CCL2 is a potent regulator of prostate cancer cell migration and proliferation. Neoplasia 2006; 8: 578-586. http://www.doi.org/10.1593/neo.06280
  25. Han IH, Kim JH, Kim SS, Ahn MH, Ryu JS. Signalling pathways associated with IL-6 production and epithelial-mesenchymal transition induction in prostate epithelial cells stimulated with Trichomonas vaginalis. Parasite Immunol 2016; 38: 678-687. http://www.doi.org/10.1111/pim.12357
  26. Miyake M, Lawton A, Goodison S, Urquidi V, Rosser CJ. Chemokine (C-X-C motif) ligand 1 (CXCL1) protein expression is increased in high-grade prostate cancer. Pathol Res Pract 2014; 210: 74-78. http://doi: 10.1016/j.prp.2013.08.013.
  27. Kuo PL, Shen KH, Hung SH, Hsu YL. CXCL1/GROα increases cell migration and invasion of prostate cancer by decreasing fibulin-1 expression through NF- κB/HDAC1 epigenetic regulation. Carcinogenesis 2012; 33: 2477-2487. http://www.doi.org/10.1093/carcin/bgs299
  28. Lu Y, Dong B, Xu F, Xu Y, Pan J, Song J, Zhang J, Huang Y, Xue W. CXCL1-LCN2 paracrine axis promotes progression of prostate cancer via the Src activation and epithelial-mesenchymal transition. Cell Commun Signal 2019; 17: 118. http://www.doi.org/10.1186/s12964-019-0434-3
  29. Hardaway AL, Herroon MK, Rajagurubandara E, Podgorski I. Marrow adipocyte-derived CXCL1 and CXCL2 contribute to osteolysis in metastatic prostate cancer. Clin Exp Metastasis 2015; 32: 353-368. http://www.doi.org/10.1007/s10585-015-9714-5