Abstract
Prostate cancer is malignant cancer leading to high mortality in the male population. The existence of suppressive cells referred to as tumor-associated macrophages (TAM) is a major obstacle in prostate cancer immunotherapy. TAMs contribute to the immunosuppressive microenvironment that promotes tumor growth and metastasis. In fact, they are main regulators of the complicated interactions between tumor and surrounding microenvironment. M2 macrophages, as a type of TAMs, are involved in the growth and progression of prostate cancer. Recently, they have gained remarkable importance as therapeutic candidates for solid tumors. In this review, we will discuss the roles of M2 macrophages and worth of their potential targeting in prostate cancer treatment. In the following, we will introduce important factors resulting in M2 macrophage promotion and also experimental therapeutic agents that may cause the inhibition of prostate cancer tumor growth.
Keywords: Prostate cancer, tumor-associated macrophage, M1/M2 macrophage, solid tumors, experimental therapeutic, suppressive cells.
Graphical Abstract
[1]
Daniyal M, Siddiqui ZA, Akram M, Asif H, Sultana S, Khan A. Epidemiology, etiology, diagnosis and treatment of prostate cancer. Asian Pac J Cancer Prev 2014; 15(22): 9575-8.
[2]
Mohsenzadegan M, Seif F, Farajollahi M, Khoshmirsafa M. Anti-oxidants as chemopreventive agents in prostate cancer: A gap between preclinical and clinical studies. Recent Patents Anticancer Drug Discov 2018; 13(2): 224-9.
[3]
Kalra R, Bhagyaraj E, Tiwari D, et al. AIRE promotes androgen-independent prostate cancer by directly regulating IL-6 and modulating tumor microenvironment. Oncogenesis 2018; 7(5): 43.
[4]
Benidir T, Hersey K, Finelli A, et al. editors. Understanding how prostate cancer patients value the current treatment options for metastatic castration resistant prostate cancer. Urol Oncol 2018; 36(5): 240.
[5]
Mohsenzadegan M, Shekarabi M, Madjd Z, et al. Study of NGEP expression pattern in cancerous tissues provides novel insights into prognostic marker in prostate cancer. Biomarkers Med 2015; 9(4): 391-401.
[6]
Mohsenzadegan M, Tajik N, Madjd Z, Shekarabi M, Farajollahi MM. Study of NGEP expression in androgen sensitive prostate cancer cells: A potential target for immunotherapy. Med J Islam Repub Iran 2015; 29: 159.
[7]
Mohsenzadegan M, Madjd Z, Asgari M, et al. Reduced expression of NGEP is associated with high-grade prostate cancers: a tissue microarray analysis. Cancer Immunol Immunother 2013; 62(10): 1609-18.
[8]
Mohsenzadegan M, Saebi F, Yazdani M, et al. Autoantibody against new gene expressed in prostate protein is traceable in prostate cancer patients. Biomarkers Med 2018; 12(10): 1125-38.
[9]
Lundholm M, Hägglöf C, Wikberg ML, et al. Secreted factors from colorectal and prostate cancer cells skew the immune response in opposite directions. Sci Rep 2015; 5: 15651.
[10]
Fujita K, Ewing CM, Sokoll LJ, et al. Cytokine profiling of prostatic fluid from cancerous prostate glands identifies cytokines associated with extent of tumor and inflammation. Prostate 2008; 68(8): 872-82.
[11]
González-Reyes S, Fernández JM, González LO, et al. Study of TLR3, TLR4, and TLR9 in prostate carcinomas and their association with biochemical recurrence. Cancer Immunol Immunother 2011; 60(2): 217-26.
[12]
Comen EA, Bowman RL, Kleppe M. Underlying causes and therapeutic targeting of the inflammatory tumor microenvironment. Front Cell Dev Biol 2018; 6: 56.
[13]
Fujii T, Shimada K, Asai O, et al. Immunohistochemical analysis of inflammatory cells in benign and precancerous lesions and carcinoma of the prostate. Pathobiol 2013; 80(3): 119-26.
[14]
Solinas G, Germano G, Mantovani A, Allavena P. Tumor‐associated macrophages (TAM) as major players of the cancer‐related inflammation. J Leukoc Biol 2009; 86(5): 1065-73.
[15]
Whiteside T. The tumor microenvironment and its role in promoting tumor growth. Oncogene 2008; 27(45): 5904.
[16]
Liu J, Li Z, Cui J, Xu G, Cui G. Cellular changes in the tumor microenvironment of human esophageal squamous cell carcinomas. Tumour Biol 2012; 33(2): 495-505.
[17]
Ohtaki Y, Ishii G, Nagai K, et al. Stromal macrophage expressing CD204 is associated with tumor aggressiveness in lung adenocarcinoma. J Thorac Oncol 2010; 5(10): 1507-15.
[18]
Murdoch C, Muthana M, Coffelt SB, Lewis CE. The role of myeloid cells in the promotion of tumour angiogenesis. Nat Rev Cancer 2008; 8(8): nrc2444.
[19]
Roca H, Varsos ZS, Sud S, et al. CCL2 and interleukin-6 promote survival of human CD11b+ peripheral blood mononuclear cells and induce M2-type macrophage polarization. J Biol Chem 2009; 284(49): 34342-54.
[20]
Ogle ME, Segar CE, Sridhar S, Botchwey EA. Monocytes and macrophages in tissue repair: Implications for immunoregenerative biomaterial design. Exp Biol Med 2016; 241(10): 1084-97.
[21]
Sharifi L, Tavakolinia N, Kiaee F, et al. A review on defects of
dendritic cells in common variable immunodeficiency. Endocrine,
Metabolic & Immune Disorders-Drug Targets (Formerly Current
Drug Targets-Immune, Endocrine & Metabolic Disorders). 2017; 17(2): 100-13.
[22]
Seif F, Khoshmirsafa M, Aazami H, et al. The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells. Cell Commun Signal 2017; 15(1): 23.
[23]
Mantovani A, Sica A. Macrophages, innate immunity and cancer: balance, tolerance, and diversity. Curr Opin Immunol 2010; 22(2): 231-7.
[24]
Ovchinnikov DA. Macrophages in the embryo and beyond: much more than just giant phagocytes. Genesis 2008; 46(9): 447-62.
[25]
Miron RJ, Bosshardt DD. OsteoMacs: Key players around bone biomaterials. Biomaterials 2016; 82: 1-19.
[26]
Raggatt LJ, Wullschleger ME, Alexander KA, et al. Fracture healing via periosteal callus formation requires macrophages for both initiation and progression of early endochondral ossification. Am J Pathol 2014; 184(12): 3192-204.
[27]
Cho SW, Soki FN, Koh AJ, et al. Osteal macrophages support physiologic skeletal remodeling and anabolic actions of parathyroid hormone in bone. Proc Natil Acad Sci 2014; 111(4): 1545-50.
[28]
Miron RJ, Zohdi H, Fujioka-Kobayashi M, Bosshardt DD. Giant cells around bone biomaterials: Osteoclasts or multi-nucleated giant cells? Acta Biomater 2016; 46: 15-28.
[29]
Jamalpoor Z, Asgari A, Lashkari MH, Mirshafiey A, Mohsenzadegan M. Modulation of macrophage polarization for bone tissue engineering applications. Iran J Allergy Asthma Immunol 2018; 17(5): 398-408.
[30]
Chang MK, Raggatt L-J, Alexander KA, et al. Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo. J Immunol 2008; 181(2): 1232-44.
[31]
Winkler IG, Sims NA, Pettit AR, et al. Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs. Blood 2010; 116(23): 4815-28.
[32]
Mantovani A, Sozzani S, Locati M, Allavena P, Sica A. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 2002; 23(11): 549-55.
[33]
Genin M, Clement F, Fattaccioli A, Raes M, Michiels C. M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide. BMC Cancer 2015; 15(1): 577.
[35]
Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol 2008; 8(12): 958-69.
[36]
Guihard P, Danger Y, Brounais B, et al. Induction of osteogenesis in mesenchymal stem cells by activated monocytes/macrophages depends on oncostatin M signaling. Stem Cells 2012; 30(4): 762-72.
[37]
Sharifi L, Mohsenzadegan M, Aghamohammadi A, et al. Immunomodulatory effect of G2013 (aL-Guluronic acid) on theTLR2 and TLR4 in human mononuclear cells. Curr Drug Discov Technol 2018; 15(2): 123-31.
[38]
Martinez FO, Helming L, Gordon S. Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol 2009; 27: 451-83.
[39]
Champagne C, Takebe J, Offenbacher S, Cooper L. Macrophage cell lines produce osteoinductive signals that include bone morphogenetic protein-2. Bone 2002; 30(1): 26-31.
[40]
Assoian RK, Fleurdelys BE, Stevenson HC, et al. Expression and secretion of type beta transforming growth factor by activated human macrophages. Proc Natl Aca Sci 1987; 84(17): 6020-4.
[41]
Takahashi F, Takahashi K, Shimizu K, et al. Osteopontin is strongly expressed by alveolar macrophages in the lungs of acute respiratory distress syndrome. Lung 2004; 182(3): 173-85.
[42]
Kreutz M, Andreesen R, Krause SW, et al. 1, 25-dihydroxyvitamin D3 production and vitamin D3 receptor expression are developmentally regulated during differentiation of human monocytes into macrophages. Blood 1993; 82(4): 1300-7.
[43]
Poh AR, Ernst M. Targeting macrophages in cancer: From bench to bedside. Front Concol 2018; 8: 49.
[44]
Rőszer T. Understanding the mysterious M2 macrophage through activation markers and effector mechanisms. Mediators Inflamm 2015; 2015: 816460.
[45]
Knipper JA, Willenborg S, Brinckmann J, et al. Interleukin-4 receptor α signaling in myeloid cells controls collagen fibril assembly in skin repair. Immunity 2015; 43(4): 803-16.
[46]
Jetten N, Verbruggen S, Gijbels MJ, et al. Anti-inflammatory M2, but not pro-inflammatory M1 macrophages promote angiogenesis in vivo. Angiogenesis 2014; 17(1): 109-18.
[47]
Murray PJ, Allen JE, Biswas SK, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 2014; 41(1): 14-20.
[48]
Wang Q, Ni H, Lan L, et al. Fra-1 protooncogene regulates IL-6 expression in macrophages and promotes the generation of M2d macrophages. Cell Res 2010; 20(6): 701-12.
[49]
Ferrante CJ, Pinhal-Enfield G, Elson G, et al. The adenosine-dependent angiogenic switch of macrophages to an M2-like phenotype is independent of interleukin-4 receptor alpha (IL-4Rα) signaling. Inflammation 2013; 36(4): 921-31.
[50]
Zarif JC, Taichman RS, Pienta KJ. TAM macrophages promote growth and metastasis within the cancer ecosystem. Oncoimmunol 2014; 3(7): e941734.
[51]
Allavena P, Sica A, Solinas G, Porta C, Mantovani A. The inflammatory micro-environment in tumor progression: the role of tumor-associated macrophages. Crit Rev Oncol Hematol 2008; 66(1): 1-9.
[52]
Rogers TL, Holen I. Tumour macrophages as potential targets of bisphosphonates. J Transl Med 2011; 9(1): 177.
[53]
Saqib U, Sarkar S, Suk K, et al. Phytochemicals as modulators of M1-M2 macrophages in inflammation. Oncotarget 2018; 9(25): 17937.
[54]
Coffelt SB, Hughes R, Lewis CE. Tumor-associated macrophages: effectors of angiogenesis and tumor progression. Biochimica et Biophysica Acta (BBA)-. Rev Can 2009; 1796(1): 11-8.
[55]
Redente EF, Dwyer-Nield LD, Merrick DT, et al. Tumor progression stage and anatomical site regulate tumor-associated macrophage and bone marrow-derived monocyte polarization. Am J Pathol 2010; 176(6): 2972-85.
[56]
Riabov V, Kim D, Chhina S, Alexander RB, Klyushnenkova EN. Immunostimulatory early phenotype of tumor-associated macrophages does not predict tumor growth outcome in an HLA-DR mouse model of prostate cancer. Cancer Immunol Immunother 2015; 64(7): 873-83.
[57]
Yang L, Wang F, Wang L, et al. CD163+ tumor-associated macrophage is a prognostic biomarker and is associated with therapeutic effect on malignant pleural effusion of lung cancer patients. Oncotarget 2015; 6(12): 10592.
[58]
Fan H-h, Li L, Zhang Y-m, et al. PKCζ in prostate cancer cells represses the recruitment and M2 polarization of macrophages in the prostate cancer microenvironment. Tumour Biol 2017; 39(6): 1010428317701442.
[59]
Dun EC, Hanley K, Wieser F, et al. Infiltration of tumor-associated macrophages is increased in the epithelial and stromal compartments of endometrial carcinomas. Int J Gynecol Pathol 2013; 32(6): 576-84.
[60]
Soki FN, Cho SW, Kim YW, et al. Bone marrow macrophages support prostate cancer growth in bone. Oncotarget 2015; 6(34): 35782.
[61]
Kim SW, Kim JS, Papadopoulos J, et al. Consistent interactions between tumor cell IL-6 and macrophage TNF-α enhance the growth of human prostate cancer cells in the bone of nude mouse. Int Immunopharmacol 2011; 11(7): 862-72.
[62]
Xu E-R, Blythe EE, Fischer G, Hyvönen M. Structural analyses of von Willebrand factor C domains of collagen 2A and CCN3 reveal an alternative mode of binding to bone morphogenetic protein-2. J Biol Chem 2017; 292(30): 12516-27.
[63]
Maillard M, Cadot B, Ball R, et al. Differential expression of the ccn3 (nov) proto-oncogene in human prostate cell lines and tissues. Mol Pathol 2001; 54(4): 275.
[64]
Chen P-C, Cheng H-C, Wang J, et al. Prostate cancer-derived CCN3 induces M2 macrophage infiltration and contributes to angiogenesis in prostate cancer microenvironment. Oncotarget 2014; 5(6): 1595.
[65]
Heilborn JD, Nilsson MF, Jimenez CIC, et al. Antimicrobial protein hCAP18/LL‐37 is highly expressed in breast cancer and is a putative growth factor for epithelial cells. Int J Cancer 2005; 114(5): 713-9.
[66]
Cha HR, Lee JH, Hensel JA, et al. Prostate cancer‐derived cathelicidin‐related antimicrobial peptide facilitates macrophage differentiation and polarization of immature myeloid progenitors to protumorigenic macrophages. Prostate 2016; 76(7): 624-36.
[67]
Yoshimura T, Howard OZ, Ito T, et al. Monocyte chemoattractant protein-1/CCL2 produced by stromal cells promotes lung metastasis of 4T1 murine breast cancer cells. PLoS One 2013; 8(3): e58791.
[68]
Deshmane SL, Kremlev S, Amini S, Sawaya BE. Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interferon Cytokine Res 2009; 29(6): 313-26.
[69]
Roca H, Varsos Z, Pienta KJ. CCL2 protects prostate cancer PC3 cells from autophagic death via phosphatidylinositol 3-kinase/AKT-dependent survivin up-regulation. J Biol Chem 2008; 283(36): 25057-73.
[70]
Kawabe K, Takano K, Moriyama M, Nakamura Y. Microglia endocytose amyloid β through the binding of transglutaminase 2 and milk fat globule EGF factor 8 protein. Neurochem Res 2018; 43(1): 32-40.
[71]
Sugano G, Bernard-Pierrot I, Lae M, et al. Milk fat globule—epidermal growth factor—factor VIII (MFGE8)/lactadherin promotes bladder tumor development. Oncogene 2011; 30(6): 642.
[72]
Hanayama R, Tanaka M, Miwa K, et al. Identification of a factor that links apoptotic cells to phagocytes. Nat 2002; 417(6885): 182.
[73]
Soki FN, Koh AJ, Jones JD, et al. Polarization of prostate cancer-associated macrophages is induced by milk fat globule-EGF factor 8 (MFG-E8)-mediated efferocytosis. J Biol Chem 2014; 289(35): 24560-72.
[74]
Chu EP, Elso CM, Pollock AH, et al. Disruption of Serinc1, which facilitates serine-derived lipid synthesis, fails to alter macrophage function, lymphocyte proliferation or autoimmune disease susceptibility. Mol Immunol 2017; 82: 19-33.
[75]
Taylor DD, Gercel-Taylor C. editors. Exosomes/microvesicles: mediators of cancer-associated immunosuppressive microenvironments. Semin Immunopathol 2011; 33(5): 441-54.
[76]
Ran S, He J, Huang X, et al. Antitumor effects of a monoclonal antibody that binds anionic phospholipids on the surface of tumor blood vessels in mice. Clin Cancer Res 2005; 11(4): 1551-62.
[77]
Yin Y, Huang X, Lynn KD, Thorpe PE. Phosphatidylserine-targeting antibody induces M1 macrophage polarization and promotes myeloid-derived suppressor cell differentiation. Cancer Immunol Res 2013; 1(4): 256-68.
[78]
Yang YJ, Lee SH, Hong SJ, Chung BC. Comparison of fatty acid profiles in the serum of patients with prostate cancer and benign prostatic hyperplasia. Clin Biochem 1999; 32(6): 405-9.
[79]
Torfadottir JE, Valdimarsdottir UA, Mucci LA, et al. Consumption of fish products across the lifespan and prostate cancer risk. PLoS One 2013; 8(4): e59799.
[80]
Liang P, Henning SM, Schokrpur S, et al. Effect of Dietary Omega‐3 Fatty Acids on Tumor‐Associated Macrophages and Prostate Cancer Progression. Prostate 2016; 76(14): 1293-302.
[81]
Li C-C, Hou Y-C, Yeh C-L, Yeh S-L. Effects of eicosapentaenoic acid and docosahexaenoic acid on prostate cancer cell migration and invasion induced by tumor-associated macrophages. PLoS One 2014; 9(6): e99630.
[82]
Rimessi A, Patergnani S, Ioannidi E, Pinton P. Chemoresistance and cancer-related inflammation: two hallmarks of cancer connected by an atypical link, PKCζ. Front Oncol 2013; 3: 232.
[83]
Kim JY, Valencia T, Abu-Baker S, et al. c-Myc phosphorylation by PKCζ represses prostate tumorigenesis. Proc Natil Acad Scie 2013; 110(16): 6418-23.
[84]
Yang S, Zhang JJ, Huang X-Y. Orai1 and STIM1 are critical for breast tumor cell migration and metastasis. Cancer Cell 2009; 15(2): 124-34.
[85]
Tse A, Lee AK, Frederick WT. Ca2+ signaling and exocytosis in pituitary corticotropes. Cell Calcium 2012; 51(3-4): 253-9.
[86]
Vig M, Peinelt C, Beck A, et al. CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry. Sci 2006; 312(5777): 1220-3.
[87]
Feske S, Gwack Y, Prakriya M, et al. A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nat 2006; 441(7090): 179.
[88]
Peinelt C, Vig M, Koomoa DL, et al. Amplification of CRAC current by STIM1 and CRACM1 (Orai1). Nat Cell Biol 2006; 8(7): 771.
[89]
Xu Y, Zhang S, Niu H, et al. STIM1 accelerates cell senescence in a remodeled microenvironment but enhances the epithelial-to-mesenchymal transition in prostate cancer. Sci Rep 2015; 5: 11754.
[90]
Armstrong A, Häggman M, Stadler W, et al. Long-term survival and biomarker correlates of tasquinimod efficacy in a multicenter randomized study of men with minimally symptomatic metastatic castration-resistant prostate cancer. Clin Cancer Res 2013; 19(24): 6891-901.
[91]
Shen L, Sundstedt A, Ciesielski M, et al. Tasquinimod modulates suppressive myeloid cells and enhances cancer immunotherapies in murine models. Cancer Immunol Res 2015; 3(2): 136-48.
[92]
Valdespino V, Tsagozis P, Pisa P. Current perspectives in the treatment of advanced prostate cancer. Med Oncol 2007; 24(3): 273-86.
[93]
Kuroda J, Kimura S, Segawa H, et al. The third-generation bisphosphonate zoledronate synergistically augments the anti-Ph+ leukemia activity of imatinib mesylate. Blood 2003; 102(6): 2229-35.
[94]
Comito G, Segura CP, Taddei ML, et al. Zoledronic acid impairs stromal reactivity by inhibiting M2-macrophages polarization and prostate cancer-associated fibroblasts. Oncotarget 2017; 8(1): 118.
[95]
Vasiliadou I, Holen I. The role of macrophages in bone metastasis. J Bone Oncol 2013; 2(4): 158-66.
[96]
Germano G, Frapolli R, Belgiovine C, et al. Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell 2013; 23(2): 249-62.
Article Metrics
94
8