Skip to main content

Advertisement

SpringerLink
Log in

Inflammation and prostate cancer: friends or foe?

  • Review
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Introduction

Prostate cancer is the most common non-cutaneous malignancy diagnosed in men. Moving from histological observations since a long time, it has been recognized that innate and adaptive immunity actively participates in the pathogenesis, surveillance, and progression of prostate cancer.

Materials and methods

A PubMed and Web of Science databases search was performed for studies providing evidence on the roles of the innate and adaptive immunity during the development and progression of prostate cancer.

Conclusions

There are growing evidences that chronic inflammation is involved in the regulation of cellular events in prostate carcinogenesis, including disruption of the immune response and regulation of the tumor microenvironment. This review discusses the role played by the innate and adaptive immune system in the local progression of prostate cancer, and the prognostic information that we can currently understand and exploit.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Shukla ME, Yu C, Reddy CA, Stephans KL, Klein EA, Abdel-Wahab M, et al. Evaluation of the current prostate cancer staging system based on cancer-specific mortality in the surveillance, epidemiology, and end results database. Clinical Genitourin Cancer. 2015;13(1):17–21 (PubMed PMID: 25571871).

    Google Scholar 

  2. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29 (PubMed PMID: 24399786).

    PubMed  Google Scholar 

  3. Loeb S, Catalona WJ. Prostate-specific antigen in clinical practice. Cancer Lett. 2007;249(1):30–9 (PubMed PMID: 17258389).

    CAS  PubMed  Google Scholar 

  4. Loeb S, Gashti SN, Catalona WJ. Exclusion of inflammation in the differential diagnosis of an elevated prostate-specific antigen (PSA). Urol Oncol. 2009;27(1):64–6 (PubMed PMID: 19111800).

    CAS  PubMed  Google Scholar 

  5. Schroder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360(13):1320–8 (PubMed PMID: 19297566).

    PubMed  Google Scholar 

  6. Presti JC Jr. Prostate biopsy strategies. Nat Clin Prac Urol. 2007;4(9):505–11 (PubMed PMID: 17823604).

    Google Scholar 

  7. Taverna G, Maffezzini M, Benetti A, Seveso M, Giusti G, Graziotti P. A single injection of lidocaine as local anesthesia for ultrasound guided needle biopsy of the prostate. J Urol. 2002;167(1):222–3 (PubMed PMID: 11743310).

    PubMed  Google Scholar 

  8. Scattoni V, Maccagnano C, Capitanio U, Gallina A, Briganti A, Montorsi F. Random biopsy: when, how many and where to take the cores?. World J Urol. 2014;32(4):859–69 (PubMed PMID: 24908067).

    PubMed  Google Scholar 

  9. Egevad L. Recent trends in Gleason grading of prostate cancer: I. Pattern interpretation. Anal Quant Cytol Histol/Int Acad Cytol Am Soc Cytol. 2008;30(4):190–8. (PubMed PMID: 18773736).

  10. Rubin MA. Targeted therapy of cancer: new roles for pathologists–prostate cancer. Modern Pathol: Off J US Can Acad Pathol, Inc. 2008;21(Suppl 2):S44–55 (PubMed PMID: 18437173).

    CAS  Google Scholar 

  11. McDunn JE, Li Z, Adam KP, Neri BP, Wolfert RL, Milburn MV, et al. Metabolomic signatures of aggressive prostate cancer. Prostate. 2013;73(14):1547–60 (PubMed PMID: 23824564).

    CAS  PubMed  Google Scholar 

  12. Schmid M, Hansen J, Rink M, Fisch M, Chun F. The development of nomograms for stratification of men at risk of prostate cancer prior to prostate biopsy. Biomark Med. 2013;7(6):843–50 (PubMed PMID: 24266817).

    CAS  PubMed  Google Scholar 

  13. Dimakakos A, Armakolas A, Koutsilieris M. Novel tools for prostate cancer prognosis, diagnosis, and follow-up. BioMed Res Int. 2014;2014:890697 (PubMed PMID: 24877145. Pubmed Central PMCID: 4024423).

    PubMed Central  PubMed  Google Scholar 

  14. Valdes-Mora F, Clark SJ. Prostate cancer epigenetic biomarkers: next-generation technologies. Oncogene. 2014;0 (PubMed PMID: 24837368).

  15. Qu M, Ren SC, Sun YH. Current early diagnostic biomarkers of prostate cancer. Asian J Androl. 2014;16(4):549–54 (PubMed PMID: 24830695).

    PubMed Central  CAS  PubMed  Google Scholar 

  16. Klotz L. Prostate cancer overdiagnosis and overtreatment. Curr Opin Endocrinol Diabetes Obes. 2013;20(3):204–9 (PubMed PMID: 23609043).

    CAS  PubMed  Google Scholar 

  17. Veeranki S. Role of inflammasomes and their regulators in prostate cancer initiation, progression and metastasis. Cell Mol Biol Lett. 2013;18(3):355–67 (PubMed PMID: 23793845).

    CAS  PubMed  Google Scholar 

  18. Orsted DD, Bojesen SE. The link between benign prostatic hyperplasia and prostate cancer. Nat Rev Urol. 2013;10(1):49–54 (PubMed PMID: 23165396).

    CAS  PubMed  Google Scholar 

  19. Nakai Y, Nonomura N. Inflammation and prostate carcinogenesis. Int J Urol: Off J Jpn Urol Assoc. 2013;20(2):150–60 (PubMed PMID: 22852773).

    CAS  Google Scholar 

  20. Taverna G, Seveso M, Giusti G, Hurle R, Graziotti P, Stifter S, et al. Senescent remodeling of the innate and adaptive immune system in the elderly men with prostate cancer. Curr Gerontol Geriatr Res. 2014;2014:478126 (PubMed PMID: 24772169. Pubmed Central PMCID: 3977481).

    PubMed Central  PubMed  Google Scholar 

  21. De Marzo AM, Platz EA, Sutcliffe S, Xu J, Gronberg H, Drake CG, et al. Inflammation in prostate carcinogenesis. Nat Rev Cancer. 2007;7(4):256–69 (PubMed PMID: 17384581. Pubmed Central PMCID: 3552388).

    PubMed Central  CAS  PubMed  Google Scholar 

  22. Ittmann M, Huang J, Radaelli E, Martin P, Signoretti S, Sullivan R, et al. Animal models of human prostate cancer: the consensus report of the New York meeting of the Mouse Models of Human Cancers Consortium Prostate Pathology Committee. Cancer Res. 2013;73(9):2718–36 (PubMed PMID: 23610450. Pubmed Central PMCID: 3644021).

    PubMed Central  CAS  PubMed  Google Scholar 

  23. Montironi R, Lopez-Beltran A, Mazzucchelli R, Scarpelli M, Galosi AB, Cheng L. Contemporary update on pathology-related issues on routine workup of prostate biopsy: sectioning, tumor extent measurement, specimen orientation, and immunohistochemistry. Anal Quant Cytol Histol/Int Acad Cytol Am Soc Cytol. 2014;36(2):61–70 (PubMed PMID: 24902358).

    Google Scholar 

  24. Ammirante M, Luo JL, Grivennikov S, Nedospasov S, Karin M. B-cell-derived lymphotoxin promotes castration-resistant prostate cancer. Nature. 2010;464(7286):302–5 (PubMed PMID: 20220849. Pubmed Central PMCID: 2866639).

    PubMed Central  CAS  PubMed  Google Scholar 

  25. Gurel B, Lucia MS, Thompson IM, Jr., Goodman PJ, Tangen CM, Kristal AR, et al. Chronic inflammation in benign prostate tissue is associated with high-grade prostate cancer in the placebo arm of the prostate cancer prevention trial. Cancer Epidemiol Biomarkers Prev: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2014;23(5):847–56. (PubMed PMID: 24748218. Pubmed Central PMCID: 4012292).

  26. Klinke DJ 2nd. An evolutionary perspective on anti-tumor immunity. Front Oncol. 2012;2:202 (PubMed PMID: 23336100. Pubmed Central PMCID: 3541690).

    PubMed Central  PubMed  Google Scholar 

  27. Chiarugi P, Paoli P, Cirri P. Tumor microenvironment and metabolism in prostate cancer. Semin Oncol. 2014;41(2):267–80 (PubMed PMID: 24787298).

    CAS  PubMed  Google Scholar 

  28. Goldstein AS, Witte ON. Does the microenvironment influence the cell types of origin for prostate cancer? Genes Dev. 2013;27(14):1539–44 (PubMed PMID: 23873937).

    PubMed Central  CAS  PubMed  Google Scholar 

  29. Sfanos KS, Hempel HA, De Marzo AM. The role of inflammation in prostate cancer. Adv Exp Med Biol. 2014;816:153–81 (PubMed PMID: 24818723).

    PubMed  Google Scholar 

  30. Vykhovanets EV, Maclennan GT, Vykhovanets OV, Gupta S. IL-17 expression by macrophages is associated with proliferative inflammatory atrophy lesions in prostate cancer patients. Int J Clin Exp Pathol. 2011;4(6):552–65. (PubMed PMID: 21904631. Pubmed Central PMCID: 3160607. Epub 2011/09/10. eng).

  31. Fang LY, Izumi K, Lai KP, Liang L, Li L, Miyamoto H, et al. Infiltrating macrophages promote prostate tumorigenesis via modulating androgen receptor-mediated CCL4-STAT3 signaling. Cancer Res. 2013;73(18):5633–46 (PubMed PMID: 23878190. PubMed Central PMCID: 3833080).

    CAS  PubMed  Google Scholar 

  32. Okada K, Kojima M, Naya Y, Kamoi K, Yokoyama K, Takamatsu T, et al. Correlation of histological inflammation in needle biopsy specimens with serum prostate-specific antigen levels in men with negative biopsy for prostate cancer. Urology. 2000;55(6):892–8 (PubMed PMID: 10840104. Epub 2000/06/07. eng).

    CAS  PubMed  Google Scholar 

  33. Pittoni P, Colombo MP. The dark side of mast cell-targeted therapy in prostate cancer. Cancer Res. 2012;72(4):831–5 (PubMed PMID: 22307838. Epub 2012/02/07. eng).

    CAS  PubMed  Google Scholar 

  34. Taverna G, Giusti G, Seveso M, Hurle R, Colombo P, Stifter S, et al. Mast cells as a potential prognostic marker in prostate cancer. Dis Markers. 2013;35(6):711–20 (PubMed PMID: 24324287. Pubmed Central PMCID: 3844173).

    PubMed Central  PubMed  Google Scholar 

  35. Globa T, Saptefrti L, Ceausu RA, Gaje P, Cimpean AM, Raica M. Mast cell phenotype in benign and malignant tumors of the prostate. Pol J Pathol: Off J Pol Soc Pathol. 2014;65(2):147–53 (PubMed PMID: 25119176).

    CAS  Google Scholar 

  36. Frankel TL, Burns W, Riley J, Morgan RA, Davis JL, Hanada K, et al. Identification and characterization of a tumor infiltrating CD56(+)/CD16(−) NK cell subset with specificity for pancreatic and prostate cancer cell lines. Cancer Immunol Immunother. 2010;59(12):1757–69 PubMed PMID: 20734041. Epub 2010/08/25. eng.

    CAS  PubMed  Google Scholar 

  37. Kryvenko ON, Jankowski M, Chitale DA, Tang D, Rundle A, Trudeau S, et al. Inflammation and preneoplastic lesions in benign prostate as risk factors for prostate cancer. Mod Pathol: Off J US Can Acad Pathol, Inc. 2012;25(7):1023–32 (PubMed PMID: 22460812. Epub 2012/03/31. eng).

    CAS  Google Scholar 

  38. Sfanos KS, De Marzo AM. Prostate cancer and inflammation: the evidence. Histopathology. 2012;60(1):199–215 (PubMed PMID: 22212087. Epub 2012/01/04. eng).

    PubMed Central  PubMed  Google Scholar 

  39. Flammiger A, Bayer F, Cirugeda-Kuhnert A, Huland H, Tennstedt P, Simon R, et al. Intratumoral T but not B lymphocytes are related to clinical outcome in prostate cancer. Apmis. 2012;120(11):901–8 (PubMed PMID: 23009114. Epub 2012/09/27. eng).

    CAS  PubMed  Google Scholar 

  40. McDowell KL, Begley LA, Mor-Vaknin N, Markovitz DM, Macoska JA. Leukocytic promotion of prostate cellular proliferation. Prostate. 2010;70(4):377–89 (Pubmed Central PMCID: 3167472. Epub 2009/10/30. eng).

    PubMed Central  CAS  PubMed  Google Scholar 

  41. Liu Y, Saeter T, Vlatkovic L, Servoll E, Waaler G, Axcrona U, et al. Dendritic and lymphocytic cell infiltration in prostate carcinoma. Histol Histopathol. 2013;28(12):1621–8 (PubMed PMID: 23729368).

    CAS  PubMed  Google Scholar 

  42. Hussein MR, Al-Assiri M, Musalam AO. Phenotypic characterization of the infiltrating immune cells in normal prostate, benign nodular prostatic hyperplasia and prostatic adenocarcinoma. Exp Mol Pathol. 2009;86(2):108–13 (PubMed PMID: 19111537).

    CAS  PubMed  Google Scholar 

  43. De Nunzio C, Kramer G, Marberger M, Montironi R, Nelson W, Schroder F, et al. The controversial relationship between benign prostatic hyperplasia and prostate cancer: the role of inflammation. Eur Urol. 2011;60(1):106–17 (PubMed PMID: 21497433).

    PubMed  Google Scholar 

  44. Lakshmi Narendra B, Eshvendar Reddy K, Shantikumar S, Ramakrishna S. Immune system: a double-edged sword in cancer. Inflamm Res: Off J Eur Hist Res Soc [et al]. 2013;62(9):823–34 (PubMed PMID: 23868500).

    CAS  Google Scholar 

  45. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–44 (PubMed PMID: 18650914).

    CAS  PubMed  Google Scholar 

  46. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420(6917):860–7 (PubMed PMID: 12490959. Pubmed Central PMCID: 2803035).

    PubMed Central  CAS  PubMed  Google Scholar 

  47. Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 2010;11(10):889–96 (PubMed PMID: 20856220).

    CAS  PubMed  Google Scholar 

  48. Mantovani A, Sica A. Macrophages, innate immunity and cancer: balance, tolerance, and diversity. Curr Opin Immunol. 2010;22(2):231–7 (PubMed PMID: 20144856).

    CAS  PubMed  Google Scholar 

  49. Sica A, Larghi P, Mancino A, Rubino L, Porta C, Totaro MG, et al. Macrophage polarization in tumour progression. Semin Cancer Biol. 2008;18(5):349–55 (PubMed PMID: 18467122).

    CAS  PubMed  Google Scholar 

  50. Lanciotti M, Masieri L, Raspollini MR, Minervini A, Mari A, Comito G, et al. The role of M1 and M2 macrophages in prostate cancer in relation to extracapsular tumor extension and biochemical recurrence after radical prostatectomy. BioMed Res Int. 2014;2014:486798 (PubMed PMID: 24738060. Pubmed Central PMCID: 3967497).

    PubMed Central  CAS  PubMed  Google Scholar 

  51. De Marzo AM, Marchi VL, Epstein JI, Nelson WG. Proliferative inflammatory atrophy of the prostate: implications for prostatic carcinogenesis. Am J Pathol. 1999;155(6):1985–92 (PubMed PMID: 10595928. Pubmed Central PMCID: 1866955).

    PubMed Central  PubMed  Google Scholar 

  52. Comito G, Giannoni E, Segura CP, Barcellos-de-Souza P, Raspollini MR, Baroni G, et al. Cancer-associated fibroblasts and M2-polarized macrophages synergize during prostate carcinoma progression. Oncogene. 2014;33(19):2423–31 (PubMed PMID: 23728338).

    CAS  PubMed  Google Scholar 

  53. Xu J, Escamilla J, Mok S, David J, Priceman S, West B, et al. CSF1R signaling blockade stanches tumor-infiltrating myeloid cells and improves the efficacy of radiotherapy in prostate cancer. Cancer Res. 2013;73(9):2782–94 (PubMed PMID: 23418320).

    PubMed Central  CAS  PubMed  Google Scholar 

  54. Fujii T, Shimada K, Asai O, Tanaka N, Fujimoto K, Hirao K, et al. Immunohistochemical analysis of inflammatory cells in benign and precancerous lesions and carcinoma of the prostate. Pathobiol: J Immunopathol Mol Cell Biol. 2013;80(3):119–26 (PubMed PMID: 23328608).

    CAS  Google Scholar 

  55. Kakehi Y, Segawa T, Wu XX, Kulkarni P, Dhir R, Getzenberg RH. Down-regulation of macrophage inhibitory cytokine-1/prostate derived factor in benign prostatic hyperplasia. Prostate. 2004;59(4):351–6 (PubMed PMID: 15065082).

    CAS  PubMed  Google Scholar 

  56. Dubey S, Vanveldhuizen P, Holzbeierlein J, Tawfik O, Thrasher JB, Karan D. Inflammation-associated regulation of the macrophage inhibitory cytokine (MIC-1) gene in prostate cancer. Oncol Lett. 2012;3(5):1166–70 (PubMed PMID: 22783412. Pubmed Central PMCID: 3389684).

    PubMed Central  CAS  PubMed  Google Scholar 

  57. Pickup M, Novitskiy S, Moses HL. The roles of TGFbeta in the tumour microenvironment. Nat Rev Cancer. 2013;13(11):788–99 (PubMed PMID: 24132110).

    PubMed Central  CAS  PubMed  Google Scholar 

  58. Vanhara P, Hampl A, Kozubik A, Soucek K. Growth/differentiation factor-15: prostate cancer suppressor or promoter? Prostate Cancer Prostatic Dis. 2012;15(4):320–8 (PubMed PMID: 22370725).

    CAS  PubMed  Google Scholar 

  59. Wang T, Welte T. Role of natural killer and Gamma-delta T cells in West Nile virus infection. Viruses. 2013;5(9):2298–310 (PubMed PMID: 24061543. Pubmed Central PMCID: 3798903).

    PubMed Central  PubMed  Google Scholar 

  60. Yuan H, Hsiao YH, Zhang Y, Wang J, Yin C, Shen R, et al. Destructive impact of T-lymphocytes, NK and Mast cells on basal cell layers: implications for tumor invasion. BMC Cancer. 2013;13:258 (PubMed PMID: 23705594. Pubmed Central PMCID: 3722065).

    PubMed Central  PubMed  Google Scholar 

  61. Jaillon S, Galdiero MR, Del Prete D, Cassatella MA, Garlanda C, Mantovani A. Neutrophils in innate and adaptive immunity. Semin Immunopathol. 2013;35(4):377–94 (PubMed PMID: 23553214).

    CAS  PubMed  Google Scholar 

  62. Fujita K, Imamura R, Tanigawa G, Nakagawa M, Hayashi T, Kishimoto N, et al. Low serum neutrophil count predicts a positive prostate biopsy. Prostate Cancer Prostatic Dis. 2012;15(4):386–90 (PubMed PMID: 22777394).

    CAS  PubMed  Google Scholar 

  63. Bekes EM, Schweighofer B, Kupriyanova TA, Zajac E, Ardi VC, Quigley JP, et al. Tumor-recruited neutrophils and neutrophil TIMP-free MMP-9 regulate coordinately the levels of tumor angiogenesis and efficiency of malignant cell intravasation. Am J Pathol. 2011;179(3):1455–70 (PubMed PMID: 21741942. Pubmed Central PMCID: 3157227).

    PubMed Central  CAS  PubMed  Google Scholar 

  64. Keizman D, Gottfried M, Ish-Shalom M, Maimon N, Peer A, Neumann A, et al. Pretreatment neutrophil-to-lymphocyte ratio in metastatic castration-resistant prostate cancer patients treated with ketoconazole: association with outcome and predictive nomogram. Oncologist. 2012;17(12):1508–14 (PubMed PMID: 22971522. Pubmed Central PMCID: 3528383).

    PubMed Central  CAS  PubMed  Google Scholar 

  65. Raval RR, Sharabi AB, Walker AJ, Drake CG, Sharma P. Tumor immunology and cancer immunotherapy: summary of the 2013 SITC primer. J Immunother Cancer. 2014;2:14 (PubMed PMID: 24883190. Pubmed Central PMCID: 4039332).

    PubMed Central  PubMed  Google Scholar 

  66. McArdle PA, Canna K, McMillan DC, McNicol AM, Campbell R, Underwood MA. The relationship between T-lymphocyte subset infiltration and survival in patients with prostate cancer. Br J Cancer. 2004;91(3):541–3 (PubMed PMID: 15266325. Pubmed Central PMCID: 2409839).

    PubMed Central  CAS  PubMed  Google Scholar 

  67. Yuan H, Wei X, Zhang G, Li C, Zhang X, Hou J. B7-H3 over expression in prostate cancer promotes tumor cell progression. J Urol. 2011;186(3):1093–9 (PubMed PMID: 21784485).

    CAS  PubMed  Google Scholar 

  68. Si TG, Wang JP, Guo Z. Analysis of circulating regulatory T cells (CD4+  CD25+  CD127−) after cryosurgery in prostate cancer. Asian J Androl. 2013;15(4):461–5 (PubMed PMID: 23728588. Pubmed Central PMCID: 3739231).

    PubMed Central  CAS  PubMed  Google Scholar 

  69. Miller AM, Lundberg K, Ozenci V, Banham AH, Hellstrom M, Egevad L, et al. CD4+ CD25high T cells are enriched in the tumor and peripheral blood of prostate cancer patients. J Immunol. 2006;177(10):7398–405 (PubMed PMID: 17082659).

    CAS  PubMed  Google Scholar 

  70. Yokokawa J, Cereda V, Remondo C, Gulley JL, Arlen PM, Schlom J, et al. Enhanced functionality of CD4+CD25(high)FoxP3+ regulatory T cells in the peripheral blood of patients with prostate cancer. Clin Cancer Res: Off J Am Assoc Cancer Res. 2008;14(4):1032–40 (PubMed PMID: 18281535).

    CAS  Google Scholar 

  71. Sfanos KS, Bruno TC, Maris CH, Xu L, Thoburn CJ, DeMarzo AM, et al. Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing. Clinical Cancer Research: Off J Am Assoc Cancer Res. 2008;14(11):3254–61 (PubMed PMID: 18519750. Pubmed Central PMCID: 3082357).

    CAS  Google Scholar 

  72. Zou L, Barnett B, Safah H, Larussa VF, Evdemon-Hogan M, Mottram P, et al. Bone marrow is a reservoir for CD4+CD25+ regulatory T cells that traffic through CXCL12/CXCR4 signals. Cancer Res. 2004;64(22):8451–5 (PubMed PMID: 15548717).

    CAS  PubMed  Google Scholar 

  73. Davidsson S, Ohlson AL, Andersson SO, Fall K, Meisner A, Fiorentino M, et al. CD4 helper T cells, CD8 cytotoxic T cells, and FOXP3(+) regulatory T cells with respect to lethal prostate cancer. Modern Pathol: Off J US Can Acad Pathol, Inc. 2013;26(3):448–55 (PubMed PMID: 23041830).

    CAS  Google Scholar 

  74. Gannon PO, Alam Fahmy M, Begin LR, Djoukhadjian A, Filali-Mouhim A, Lapointe R, et al. Presence of prostate cancer metastasis correlates with lower lymph node reactivity. Prostate. 2006;66(16):1710–20 (PubMed PMID: 16955408).

    PubMed  Google Scholar 

  75. Vindrieux D, Escobar P, Lazennec G. Emerging roles of chemokines in prostate cancer. Endocr Relat Cancer. 2009;16(3):663–73 (PubMed PMID: 19556286).

    CAS  PubMed  Google Scholar 

  76. Balkwill FR. The chemokine system and cancer. J Pathol. 2012;226(2):148–57 (PubMed PMID: 21989643).

    CAS  PubMed  Google Scholar 

  77. Vendramini-Costa DB, Carvalho JE. Molecular link mechanisms between inflammation and cancer. Curr Pharm Des. 2012;18(26):3831–52 (PubMed PMID: 22632748).

    CAS  PubMed  Google Scholar 

  78. Salazar N, Castellan M, Shirodkar SS, Lokeshwar BL. Chemokines and chemokine receptors as promoters of prostate cancer growth and progression. Critical Rev Eukaryot Gene Expr. 2013;23(1):77–91 (PubMed PMID: 23557339. Pubmed Central PMCID: 3736734).

    CAS  Google Scholar 

  79. Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 2013;14(10):1014–22 (PubMed PMID: 24048123. Pubmed Central PMCID: 4118725).

    PubMed Central  CAS  PubMed  Google Scholar 

  80. Bonecchi R, Galliera E, Borroni EM, Corsi MM, Locati M, Mantovani A. Chemokines and chemokine receptors: an overview. Front Biosci. 2009;14:540–51 (PubMed PMID: 19273084).

    CAS  Google Scholar 

  81. Mantovani A, Savino B, Locati M, Zammataro L, Allavena P, Bonecchi R. The chemokine system in cancer biology and therapy. Cytokine Growth Factor Rev. 2010;21(1):27–39 (PubMed PMID: 20004131).

    CAS  PubMed  Google Scholar 

  82. Chow MT, Luster AD. Chemokines in cancer. Cancer Immunol Res. 2014;2(12):1125–31 (PubMed PMID: 25480554. Pubmed Central PMCID: 4258879).

    CAS  PubMed  Google Scholar 

  83. Allavena P, Germano G, Marchesi F, Mantovani A. Chemokines in cancer related inflammation. Exp Cell Res. 2011;317(5):664–73 (PubMed PMID: 21134366).

    CAS  PubMed  Google Scholar 

  84. Koizumi K, Hojo S, Akashi T, Yasumoto K, Saiki I. Chemokine receptors in cancer metastasis and cancer cell-derived chemokines in host immune response. Cancer Sci. 2007;98(11):1652–8 (PubMed PMID: 17894551).

    CAS  PubMed  Google Scholar 

  85. Ben-Baruch A. Organ selectivity in metastasis: regulation by chemokines and their receptors. Clin Exp Metastasis. 2008;25(4):345–56 (PubMed PMID: 17891505).

    CAS  PubMed  Google Scholar 

  86. Zlotnik A, Burkhardt AM, Homey B. Homeostatic chemokine receptors and organ-specific metastasis. Nat Rev Immunol. 2011;11(9):597–606 (PubMed PMID: 21866172).

    CAS  PubMed  Google Scholar 

  87. Wu Q, Dhir R, Wells A. Altered CXCR3 isoform expression regulates prostate cancer cell migration and invasion. Mol Cancer. 2012;11:3 (PubMed PMID: 22236567. Pubmed Central PMCID: 3320557).

    PubMed Central  CAS  PubMed  Google Scholar 

  88. Gillies K, Wertman J, Charette N, Dupre DJ. Anterograde trafficking of CXCR4 and CCR2 receptors in a prostate cancer cell line. Cell Physiol Biochem: Int J Exper Cell Physiol Biochem Pharmacol. 2013;32(1):74–85 (PubMed PMID: 23839224).

    CAS  Google Scholar 

  89. Kato T, Fujita Y, Nakane K, Mizutani K, Terazawa R, Ehara H, et al. CCR1/CCL5 interaction promotes invasion of taxane-resistant PC3 prostate cancer cells by increasing secretion of MMPs 2/9 and by activating ERK and Rac signaling. Cytokine. 2013;64(1):251–7 (PubMed PMID: 23876400).

    CAS  PubMed  Google Scholar 

  90. Zhu F, Liu P, Li J, Zhang Y. Eotaxin-1 promotes prostate cancer cell invasion via activation of the CCR3-ERK pathway and upregulation of MMP-3 expression. Oncol Rep. 2014;31(5):2049–54 (PubMed PMID: 24604010).

    CAS  PubMed  Google Scholar 

  91. Lam C, Pavel MA, Kashyap P, Salehi-Najafabadi Z, Valentino V, Yu Y. Detection of CXCR2 cytokine receptor surface expression using immunofluorescence. Methods Mol Biol. 2014;1172:193–200 (PubMed PMID: 24908306).

    PubMed  Google Scholar 

  92. Peng C, Zhou K, An S, Yang J. The effect of CCL19/CCR7 on the proliferation and migration of cell in prostate cancer. Tumour Biol: J Int Soc Oncodevelop Biol Med. 2015;36(1):329–35 (PubMed PMID: 25256673).

    CAS  Google Scholar 

  93. Maxwell PJ, Neisen J, Messenger J, Waugh DJ. Tumor-derived CXCL8 signaling augments stroma-derived CCL2-promoted proliferation and CXCL12-mediated invasion of PTEN-deficient prostate cancer cells. Oncotarget. 2014;5(13):4895–908 (PubMed PMID: 24970800. Pubmed Central PMCID: 4148108).

    PubMed Central  PubMed  Google Scholar 

  94. Culig Z. CXCL8, an underestimated “bad guy” in prostate cancer. Eur Urol. 2013;64(2):189–90 (discussion 90-2. PubMed PMID: 23000087).

    CAS  PubMed  Google Scholar 

  95. Benelli R, Stigliani S, Minghelli S, Carlone S, Ferrari N. Impact of CXCL1 overexpression on growth and invasion of prostate cancer cell. Prostate. 2013;73(9):941–51 (PubMed PMID: 23334998).

    CAS  PubMed  Google Scholar 

  96. Lin TH, Liu HH, Tsai TH, Chen CC, Hsieh TF, Lee SS, et al. CCL2 increases alphavbeta3 integrin expression and subsequently promotes prostate cancer migration. Biochim Biophys Acta. 2013;1830(10):4917–27 (PubMed PMID: 23845726).

    CAS  PubMed  Google Scholar 

  97. Fang LY, Izumi K, Lai KP, Liang L, Li L, Miyamoto H, et al. Infiltrating macrophages promote prostate tumorigenesis via modulating androgen receptor-mediated CCL4-STAT3 signaling. Cancer research. 2013;73(18):5633–46 (PubMed PMID: 23878190. Pubmed Central PMCID: 3833080).

    CAS  PubMed  Google Scholar 

  98. Ammirante M, Shalapour S, Kang Y, Jamieson CA, Karin M. Tissue injury and hypoxia promote malignant progression of prostate cancer by inducing CXCL13 expression in tumor myofibroblasts. Proc Natl Acad Sci USA. 2014;111(41):14776–81 (PubMed PMID: 25267627. Pubmed Central PMCID: 4205637).

    CAS  PubMed  Google Scholar 

  99. Chen G, Liang YX, Zhu JG, Fu X, Chen YF, Mo RJ, et al. CC chemokine ligand 18 correlates with malignant progression of prostate cancer. BioMed Res Int. 2014;2014:230183 (PubMed PMID: 25197632. Pubmed Central PMCID: 4150478).

    PubMed Central  PubMed  Google Scholar 

  100. Singh RK, Lokeshwar BL. The IL-8-regulated chemokine receptor CXCR7 stimulates EGFR signaling to promote prostate cancer growth. Cancer Res. 2011;71(9):3268–77 (PubMed PMID: 21398406. Pubmed Central PMCID: 3085571).

    PubMed Central  CAS  PubMed  Google Scholar 

  101. Ellem SJ, Taylor RA, Furic L, Larsson O, Frydenberg M, Pook D, et al. A pro-tumourigenic loop at the human prostate tumour interface orchestrated by oestrogen, CXCL12 and mast cell recruitment. J Pathol. 2014;234(1):86–98 (PubMed PMID: 25042571).

    CAS  PubMed  Google Scholar 

  102. Lin WJ, Izumi K. Androgen receptor, ccl2, and epithelial-mesenchymal transition: A dangerous affair in the tumor microenvironment. Oncoimmunology. 2014;3:e27871 (PubMed PMID: 25339999. Pubmed Central PMCID: 4203538).

    PubMed Central  PubMed  Google Scholar 

  103. Izumi K, Fang LY, Mizokami A, Namiki M, Li L, Lin WJ, et al. Targeting the androgen receptor with siRNA promotes prostate cancer metastasis through enhanced macrophage recruitment via CCL2/CCR2-induced STAT3 activation. EMBO Mol Med. 2013;5(9):1383–401 (PubMed PMID: 23982944. Pubmed Central PMCID: 3799493).

    PubMed Central  CAS  PubMed  Google Scholar 

  104. Bao BY, Yao J, Lee YF. 1alpha, 25-dihydroxyvitamin D3 suppresses interleukin-8-mediated prostate cancer cell angiogenesis. Carcinogenesis. 2006;27(9):1883–93 (PubMed PMID: 16624828).

    CAS  PubMed  Google Scholar 

  105. Velonas VM, Woo HH, dos Remedios CG, Assinder SJ. Current status of biomarkers for prostate cancer. Int J Mol Sci. 2013;14(6):11034–60 (PubMed PMID: 23708103. Pubmed Central PMCID: 3709717).

    PubMed Central  PubMed  Google Scholar 

  106. Balk SP, Ko YJ, Bubley GJ. Biology of prostate-specific antigen. J Clin Oncol. 2003;21(2):383–91 (PubMed PMID: 12525533).

    CAS  PubMed  Google Scholar 

  107. Makarov DV, Loeb S, Getzenberg RH, Partin AW. Biomarkers for prostate cancer. Annu Rev Med. 2009;60:139–51 (PubMed PMID: 18947298).

    CAS  PubMed  Google Scholar 

  108. Tsaur I, Noack A, Makarevic J, Oppermann E, Waaga-Gasser AM, Gasser M, et al. CCL2 chemokine as a potential biomarker for prostate cancer: a pilot study. Cancer Res Treat: Off J Korean Cancer Assoc. 2014. doi:10.4143/crt.2014.015 (PubMed PMID: 25483747).

  109. Xu Y, Zhang L, Sun SK, Zhang X. CC chemokine ligand 18 and IGF-binding protein 6 as potential serum biomarkers for prostate cancer. Tohoku J Exper Med. 2014;233(1):25–31 (PubMed PMID: 24747338).

    CAS  Google Scholar 

  110. Sharma J, Gray KP, Harshman LC, Evan C, Nakabayashi M, Fichorova R, et al. Elevated IL-8, TNF-alpha, and MCP-1 in men with metastatic prostate cancer starting androgen-deprivation therapy (ADT) are associated with shorter time to castration-resistance and overall survival. Prostate. 2014;74(8):820–8 (PubMed PMID: 24668612).

    CAS  PubMed  Google Scholar 

  111. Agarwal M, He C, Siddiqui J, Wei JT, Macoska JA. CCL11 (eotaxin-1): a new diagnostic serum marker for prostate cancer. Prostate. 2013;73(6):573–81 (PubMed PMID: 23059958. Pubmed Central PMCID: 3594486).

    PubMed Central  CAS  PubMed  Google Scholar 

  112. 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(2):74–8 (PubMed PMID: 24252309).

    CAS  PubMed  Google Scholar 

  113. Bostwick DG, Burke HB, Djakiew D, Euling S, Ho SM, Landolph J, et al. Human prostate cancer risk factors. Cancer. 2004;101(10 Suppl):2371–490 (PubMed PMID: 15495199).

    CAS  PubMed  Google Scholar 

  114. Wallace TA, Prueitt RL, Yi M, Howe TM, Gillespie JW, Yfantis HG, et al. Tumor immunobiological differences in prostate cancer between African-American and European-American men. Cancer Res. 2008;68(3):927–36 (PubMed PMID: 18245496).

    CAS  PubMed  Google Scholar 

  115. Isman FK, Kucukgergin C, Dasdemir S, Cakmakoglu B, Sanli O, Seckin S. Association between SDF1-3′A or CXCR4 gene polymorphisms with predisposition to and clinicopathological characteristics of prostate cancer with or without metastases. Mol Biol Rep. 2012;39(12):11073–9 (PubMed PMID: 23053994).

    CAS  PubMed  Google Scholar 

  116. Mandal RK, Agrawal T, Mittal RD. Genetic variants of chemokine CCL2 and chemokine receptor CCR2 genes and risk of prostate cancer. Tumour Biol: J Int Soc Oncodevelopment Biol Med. 2015;36(1):375–81 (PubMed PMID: 25266801).

    CAS  Google Scholar 

  117. Kirk PS, Koreckij T, Nguyen HM, Brown LG, Snyder LA, Vessella RL, et al. Inhibition of CCL2 signaling in combination with docetaxel treatment has profound inhibitory effects on prostate cancer growth in bone. Int J Mol Sci. 2013;14(5):10483–96 (PubMed PMID: 23698775. Pubmed Central PMCID: 3676850).

    PubMed Central  PubMed  Google Scholar 

  118. Zhang J, Patel L, Pienta KJ. Targeting chemokine (C-C motif) ligand 2 (CCL2) as an example of translation of cancer molecular biology to the clinic. Prog Mol Biol Transl Sci. 2010;95:31–53 (PubMed PMID: 21075328. Pubmed Central PMCID: 3197817).

    PubMed Central  CAS  PubMed  Google Scholar 

  119. Zhang J, Lu Y, Pienta KJ. Multiple roles of chemokine (C-C motif) ligand 2 in promoting prostate cancer growth. J Natl Cancer Inst. 2010;102(8):522–8 (PubMed PMID: 20233997. Pubmed Central PMCID: 2857800).

    PubMed Central  CAS  PubMed  Google Scholar 

  120. Arnatt CK, Adams JL, Zhang Z, Haney KM, Li G, Zhang Y. Design, syntheses, and characterization of piperazine based chemokine receptor CCR5 antagonists as anti prostate cancer agents. Bioorg Med Chem Lett. 2014;24(10):2319–23 (PubMed PMID: 24731275).

    CAS  PubMed  Google Scholar 

  121. Arnatt CK, Zaidi SA, Zhang Z, Li G, Richardson AC, Ware JL, et al. Design, syntheses, and characterization of pharmacophore based chemokine receptor CCR5 antagonists as anti prostate cancer agents. Eur J Med Chem. 2013;69:647–58 (PubMed PMID: 24095757).

    CAS  PubMed  Google Scholar 

  122. Bhardwaj A, Srivastava SK, Singh S, Arora S, Tyagi N, Andrews J, et al. CXCL12/CXCR4 signaling counteracts docetaxel-induced microtubule stabilization via p21-activated kinase 4-dependent activation of LIM domain kinase 1. Oncotarget. 2014;5(22):11490–500 (PubMed PMID: 25359780. Pubmed Central PMCID: 4294337).

    PubMed Central  PubMed  Google Scholar 

  123. Domanska UM, Timmer-Bosscha H, Nagengast WB, Oude Munnink TH, Kruizinga RC, Ananias HJ, et al. CXCR4 inhibition with AMD3100 sensitizes prostate cancer to docetaxel chemotherapy. Neoplasia. 2012;14(8):709–18 (PubMed PMID: 22952424. Pubmed Central PMCID: 3431178).

    PubMed Central  CAS  PubMed  Google Scholar 

  124. Rhee YH, Chung PS, Kim SH, Ahn JC. CXCR4 and PTEN are involved in the anti-metastatic regulation of anethole in DU145 prostate cancer cells. Biochem Biophys Res Commun. 2014;447(4):557–62 (PubMed PMID: 24525130).

    CAS  PubMed  Google Scholar 

  125. Mackinnon AC, Yan BC, Joseph LJ, Al-Ahmadie HA. Molecular biology underlying the clinical heterogeneity of prostate cancer: an update. Arch Pathol Lab Med. 2009;133(7):1033–40 (PubMed PMID: 19642730. Epub 2009/08/01. eng).

    CAS  PubMed  Google Scholar 

  126. Gerlinger M, Catto JW, Orntoft TF, Real FX, Zwarthoff EC, Swanton C. Intratumour heterogeneity in urologic cancers: from molecular evidence to clinical implications. Eur Urol. 2015;67(4):729–37 (PubMed PMID: 24836153).

    CAS  PubMed  Google Scholar 

  127. Demichelis F, Stanford JL. Genetic predisposition to prostate cancer: Update and future perspectives. Urol Oncol. 2015;33(2):75–84 (PubMed PMID: 24996773).

    PubMed  Google Scholar 

  128. Franco OE, Hayward SW. Targeting the tumor stroma as a novel therapeutic approach for prostate cancer. Adv Pharmacol. 2012;65:267–313 (PubMed PMID: 22959029. Epub 2012/09/11. eng).

    CAS  PubMed  Google Scholar 

  129. Iacopino F, Angelucci C, Sica G. Interactions between normal human fibroblasts and human prostate cancer cells in a co-culture system. Anticancer Res. 2012;32(5):1579–88 (PubMed PMID: 22593435. Epub 2012/05/18. eng).

    PubMed  Google Scholar 

  130. Parrinello S, Coppe JP, Krtolica A, Campisi J. Stromal-epithelial interactions in aging and cancer: senescent fibroblasts alter epithelial cell differentiation. J Cell Sci. 2005;118(Pt 3):485–96 (PubMed PMID: 15657080. Epub 2005/01/20. eng).

    CAS  PubMed  Google Scholar 

  131. Gharaee-Kermani M, Kasina S, Moore BB, Thomas D, Mehra R, Macoska JA. CXC-type chemokines promote myofibroblast phenoconversion and prostatic fibrosis. PloS one. 2012;7(11):e49278 (PubMed PMID: 23173053. Pubmed Central PMCID: 3500280).

    PubMed Central  CAS  PubMed  Google Scholar 

  132. Mimeault M, Batra SK. Development of animal models underlining mechanistic connections between prostate inflammation and cancer. World J Clin Oncol. 2013;4(1):4–13 (PubMed PMID: 23539141. Pubmed Central PMCID: 3609015).

    PubMed Central  PubMed  Google Scholar 

  133. Gutkin DW, Shurin MR. Clinical evaluation of systemic and local immune responses in cancer: time for integration. Cancer Immunol Immunother. 2014;63(1):45–57 (PubMed PMID: 24100804. Pubmed Central PMCID: 4018188).

    PubMed Central  CAS  PubMed  Google Scholar 

  134. Fridman WH, Pages F, Sautes-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012;12(4):298–306 (PubMed PMID: 22419253).

    CAS  PubMed  Google Scholar 

  135. Vignozzi L, Maggi M. Prostate cancer: intriguing data on inflammation and prostate cancer. Nat Rev Urol. 2014;11(7):369–70 (PubMed PMID: 24980193).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy

    Gianluigi Taverna

  2. Department of Immunology and Inflammation, Humanitas Clinical and Research Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy

    Elisa Pedretti, Giuseppe Di Caro, Federica Marchesi & Fabio Grizzi

  3. Department of Biotechnology and Translational Medicine, University of Milan, Milan, Italy

    Elena Monica Borroni

Authors
  1. Gianluigi Taverna
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elisa Pedretti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giuseppe Di Caro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elena Monica Borroni
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Federica Marchesi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fabio Grizzi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fabio Grizzi.

Additional information

Responsible Editor: John Di Battista.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Taverna, G., Pedretti, E., Di Caro, G. et al. Inflammation and prostate cancer: friends or foe?. Inflamm. Res. 64, 275–286 (2015). https://doi.org/10.1007/s00011-015-0812-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-015-0812-2

Keywords

Search

Navigation