Beyond Promoter: The Role of Macrophage in Invasion and Progression of Renal Cell Carcinoma

Author(s): Haibao Zhang, Guodong Zhu*

Journal Name: Current Stem Cell Research & Therapy

Volume 15 , Issue 7 , 2020

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Abstract:

Renal cell carcinoma (RCC) is one of the common urologic neoplasms, and its incidence has been increasing over the past several decades; however, its pathogenesis is still unknown up to now. Recent studies have found that in addition to tumor cells, other cells in the tumor microenvironment also affect the biological behavior of the tumor. Among them, macrophages exist in a large amount in tumor microenvironment, and they are generally considered to play a key role in promoting tumorigenesis. Therefore, we summarized the recent researches on macrophage in the invasiveness and progression of RCC in latest years, and we also introduced and discussed many studies about macrophage in RCC to promote angiogenesis by changing tumor microenvironment and inhibit immune response in order to activate tumor progression. Moreover, macrophage interactes with various cytokines to promote tumor proliferation, invasion and metastasis, and it also promotes tumor stem cell formation and induces drug resistance in the progression of RCC. The highlight of this review is to make a summary of the roles of macrophage in the invasion and progression of RCC; at the same time to raise some potential and possible targets for future RCC therapy.

Keywords: Macrophage, renal cell carcinoma, invasion, progression, cytokines, angiogenesis.

[1]
Cohen HT, McGovern FJ. Renal-cell carcinoma. N Engl J Med 2005; 353(23): 2477-90.
[http://dx.doi.org/10.1056/NEJMra043172] [PMID: 16339096]
[2]
Shuch B, Amin A, Armstrong AJ, et al. Understanding pathologic variants of renal cell carcinoma: distilling therapeutic opportunities from biologic complexity. Eur Urol 2015; 67(1): 85-97.
[http://dx.doi.org/10.1016/j.eururo.2014.04.029] [PMID: 24857407]
[3]
Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017; 67(1): 7-30.
[http://dx.doi.org/10.3322/caac.21387] [PMID: 28055103]
[4]
Mickley A, Kovaleva O, Kzhyshkowska J, Gratchev A. Molecular and immunologic markers of kidney cancer-potential applications in predictive, preventive and personalized medicine. EPMA J 2015; 6: 20.
[http://dx.doi.org/10.1186/s13167-015-0042-2] [PMID: 26500709]
[5]
Paul R, Mordhorst J, Busch R, Leyh H, Hartung R. Adrenal sparing surgery during radical nephrectomy in patients with renal cell cancer: a new algorithm. J Urol 2001; 166(1): 59-62.
[http://dx.doi.org/10.1016/S0022-5347(05)66076-4] [PMID: 11435823]
[6]
Blom JH, van Poppel H, Maréchal JM, et al. EORTC Genitourinary Tract Cancer Group. Radical nephrectomy with and without lymph-node dissection: final results of European Organization for Research and Treatment of Cancer (EORTC) randomized phase 3 trial 30881. Eur Urol 2009; 55(1): 28-34.
[http://dx.doi.org/10.1016/j.eururo.2008.09.052] [PMID: 18848382]
[7]
Guy L, Bay JO, Bastide C, Mahammedi H, Bruyere F, Karsenty G. [Medical treatment of renal cell carcinoma] Prog Urol 2013; 23(15): 1225-37.
[http://dx.doi.org/10.1016/j.purol.2013.09.011] [PMID: 24183081]
[8]
Selvarajah J, Nathawat K, Moumen A, Ashcroft M, Carroll VA. Chemotherapy-mediated p53-dependent DNA damage response in clear cell renal cell carcinoma: role of the mTORC1/2 and hy-poxia-inducible factor pathways. Cell Death Dis 2013.
[9]
Buti S, Bersanelli M, Sikokis A, et al. Chemotherapy in metastatic renal cell carcinoma today? A systematic review. Anticancer Drugs 2013; 24(6): 535-54.
[PMID: 23552469]
[10]
McDermott DF. Immunotherapy and targeted therapy combinations in renal cancer. Curr Clin Pharmacol 2011; 6(3): 207-13.
[http://dx.doi.org/10.2174/157488411797189451] [PMID: 21827391]
[11]
Coppin C. Immunotherapy for renal cell cancer in the era of targeted therapy. Expert Rev Anticancer Ther 2008; 8(6): 907-19.
[http://dx.doi.org/10.1586/14737140.8.6.907] [PMID: 18533800]
[12]
Dutcher JP. Current status of interleukin-2 therapy for metastatic renal cell carcinoma and metastatic melanoma. Oncology (Williston Park) 2002; 16(11): 4-10.
[13]
Tartour E, Mathiot C, Fridman WH. Current status of interleukin-2 therapy in cancer. Biomed Pharmacother 1992; 46(10): 473-84.
[http://dx.doi.org/10.1016/0753-3322(92)90005-R] [PMID: 1306361]
[14]
Su D, Stamatakis L, Singer EA, Srinivasan R. Renal cell carcinoma: molecular biology and targeted therapy. Curr Opin Oncol 2014; 26(3): 321-7.
[http://dx.doi.org/10.1097/CCO.0000000000000069] [PMID: 24675233]
[15]
Mattei J, da Silva RD, Sehrt D, Molina WR, Kim FJ. Targeted therapy in metastatic renal carcinoma. Cancer Lett 2014; 343(2): 156-60.
[http://dx.doi.org/10.1016/j.canlet.2013.09.038]
[16]
Clark PE. Recent advances in targeted therapy for renal cell carcinoma. Curr Opin Urol 2007; 17(5): 331-6.
[http://dx.doi.org/10.1097/MOU.0b013e3282c508e0] [PMID: 17762626]
[17]
Favaro JP, George DJ. Targeted therapy in renal cell carcinoma. Expert Opin Investig Drugs 2005; 14(10): 1251-8.
[http://dx.doi.org/10.1517/13543784.14.10.1251] [PMID: 16185167]
[18]
Barata PC, Rini BI. Treatment of renal cell carcinoma: Current status and future directions. CA Cancer J Clin 2017; 67(6): 507-24.
[http://dx.doi.org/10.3322/caac.21411] [PMID: 28961310]
[19]
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144(5): 646-74.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[20]
De Vlaeminck Y, González-Rascón A, Goyvaerts C, Breckpot K. Cancer-Associated Myeloid Regulatory Cells. Front Immunol 2016; 7: 113.
[http://dx.doi.org/10.3389/fimmu.2016.00113] [PMID: 27065074]
[21]
Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med 2013; 19(11): 1423-37.
[http://dx.doi.org/10.1038/nm.3394] [PMID: 24202395]
[22]
Turajlic S, Xu H, Litchfield K, et al. PEACE; TRACERx Renal Consortium. Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal. Cell 2018; 173(3): 581-594.e12.
[http://dx.doi.org/10.1016/j.cell.2018.03.057] [PMID: 29656895]
[23]
De I, Steffen MD, Clark PA, et al. Csf1 overexpression promotes high-grade glioma formation without impacting the polarization status of glioma associated microglia and macrophages. Cancer Res 2016; 76(9): 2552-60.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-2386] [PMID: 27013192]
[24]
Linde N, Lederle W, Depner S, van Rooijen N, Gutschalk CM, Mueller MM. Vascular endothelial growth factor-induced skin carcinogenesis depends on recruitment and alternative activation of macrophages. J Pathol 2012; 227(1): 17-28.
[http://dx.doi.org/10.1002/path.3989] [PMID: 22262122]
[25]
Su S, Liu Q, Chen J, et al. A positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis. Cancer Cell 2014; 25(5): 605-20.
[http://dx.doi.org/10.1016/j.ccr.2014.03.021] [PMID: 24823638]
[26]
Mota JM, Leite CA, Souza LE, et al. Post-sepsis state induces tumor-associated macrophage accumulation through CXCR4/CXCL12 and favors tumor progression in mice. Cancer Immunol Res 2016; 4(4): 312-22.
[http://dx.doi.org/10.1158/2326-6066.CIR-15-0170] [PMID: 26817997]
[27]
Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010; 140(6): 883-99.
[http://dx.doi.org/10.1016/j.cell.2010.01.025] [PMID: 20303878]
[28]
Zhao P, Gao D, Wang Q, et al. Response gene to complement 32 (RGC-32) expression on M2-polarized and tumor-associated macrophages is M-CSF-dependent and enhanced by tumor-derived IL-4. Cell Mol Immunol 2015; 12(6): 692-9.
[http://dx.doi.org/10.1038/cmi.2014.108] [PMID: 25418473]
[29]
Yamada K, Uchiyama A, Uehara A, et al. MFG-E8 Drives Melanoma Growth by Stimulating Mesenchymal Stromal Cell-Induced Angiogenesis and M2 Polarization of Tumor-Associated Macrophages. Cancer Res 2016; 76(14): 4283-92.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-2812] [PMID: 27197197]
[30]
Rhee I. Diverse macrophages polarization in tumor microenvironment. Arch Pharm Res 2016; 39(11): 1588-96.
[http://dx.doi.org/10.1007/s12272-016-0820-y] [PMID: 27562774]
[31]
Ugel S, De Sanctis F, Mandruzzato S, Bronte V. Tumor-induced myeloid deviation: when myeloid-derived suppressor cells meet tumor-associated macrophages. J Clin Invest 2015; 125(9): 3365-76.
[http://dx.doi.org/10.1172/JCI80006] [PMID: 26325033]
[32]
Berraondo P, Minute L, Ajona D, Corrales L, Melero I, Pio R. Innate immune mediators in cancer: between defense and resistance. Immunol Rev 2016; 274(1): 290-306.
[http://dx.doi.org/10.1111/imr.12464] [PMID: 27782320]
[33]
Yang L, Zhang Y. Tumor-associated macrophages: from basic research to clinical application. J Hematol Oncol 2017; 10(1): 58.
[http://dx.doi.org/10.1186/s13045-017-0430-2] [PMID: 28241846]
[34]
Kim S, Takahashi H, Lin WW, et al. Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature 2009; 457(7225): 102-6.
[http://dx.doi.org/10.1038/nature07623] [PMID: 19122641]
[35]
Greten FR, Karin M. The IKK/NF-kappaB activation pathway-a target for prevention and treatment of cancer. Cancer Lett 2004; 206(2): 193-9.
[http://dx.doi.org/10.1016/j.canlet.2003.08.029] [PMID: 15013524]
[36]
Ojalvo LS, King W, Cox D, Pollard JW. High-density gene expression analysis of tumor-associated macrophages from mouse mammary tumors. Am J Pathol 2009; 174(3): 1048-64.
[http://dx.doi.org/10.2353/ajpath.2009.080676] [PMID: 19218341]
[37]
Kuang DM, Zhao Q, Peng C, et al. Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1. J Exp Med 2009; 206(6): 1327-37.
[http://dx.doi.org/10.1084/jem.20082173] [PMID: 19451266]
[38]
Bingle L, Brown NJ, Lewis CE. The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol 2002; 196(3): 254-65.
[http://dx.doi.org/10.1002/path.1027] [PMID: 11857487]
[39]
Chen J, Yao Y, Gong C, et al. CCL18 from tumor-associated macrophages promotes breast cancer metastasis via PITPNM3. Cancer Cell 2011; 19(4): 541-55.
[http://dx.doi.org/10.1016/j.ccr.2011.02.006] [PMID: 21481794]
[40]
Sangaletti S, Di Carlo E, Gariboldi S, et al. Macrophage-derived SPARC bridges tumor cell-extracellular matrix interactions toward metastasis. Cancer Res 2008; 68(21): 9050-9.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-1327] [PMID: 18974151]
[41]
Tomita T, Sakurai Y, Ishibashi S, Maru Y. Imbalance of Clara cell-mediated homeostatic inflammation is involved in lung metastasis. Oncogene 2011; 30(31): 3429-39.
[http://dx.doi.org/10.1038/onc.2011.53] [PMID: 21399660]
[42]
Wang F, Yang L, Gao Q, et al. CD163+CD14+ macrophages, a potential immune biomarker for malignant pleural effusion. Cancer Immunol Immunother 2015; 64(8): 965-76.
[http://dx.doi.org/10.1007/s00262-015-1701-9] [PMID: 25944005]
[43]
Tang X. Tumor-associated macrophages as potential diagnostic and prognostic biomarkers in breast cancer. Cancer Lett 2013; 332(1): 3-10.
[http://dx.doi.org/10.1016/j.canlet.2013.01.024] [PMID: 23348699]
[44]
Adams DL, Martin SS, Alpaugh RK, et al. Circulating giant macrophages as a potential biomarker of solid tumors. Proc Natl Acad Sci USA 2014; 111(9): 3514-9.
[http://dx.doi.org/10.1073/pnas.1320198111] [PMID: 24550495]
[45]
Shigeoka M, Urakawa N, Nakamura T, et al. Tumor associated macrophage expressing CD204 is associated with tumor aggressiveness of esophageal squamous cell carcinoma. Cancer Sci 2013; 104(8): 1112-9.
[http://dx.doi.org/10.1111/cas.12188] [PMID: 23648122]
[46]
Kim KJ, Wen XY, Yang HK, Kim WH, Kang GH. Prognostic implication of m2 macrophages are determined by the propor-tional balance of tumor associated macrophages and tumor infil-trating lymphocytes in microsatellite-unstable gastric carcinoma. PLoS One 2015; 10(12)e0144192
[http://dx.doi.org/10.1371/journal.pone.0144192] [PMID: 26714314]
[47]
Boström MM, Irjala H, Mirtti T, et al. Tumor-Associated Macrophages Provide Significant Prognostic Information in Urothelial Bladder Cancer. PLoS One 2015; 10(7)e0133552
[http://dx.doi.org/10.1371/journal.pone.0133552] [PMID: 26197470]
[48]
Pienta KJ, Machiels JP, Schrijvers D, et al. Phase 2 study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 (CCL2), in metastatic castration-resistant prostate cancer. Invest New Drugs 2013; 31(3): 760-8.
[http://dx.doi.org/10.1007/s10637-012-9869-8] [PMID: 22907596]
[49]
Brana I, Calles A, LoRusso PM, et al. Carlumab, an anti-C-C chemokine ligand 2 monoclonal antibody, in combination with four chemotherapy regimens for the treatment of patients with solid tumors: an open-label, multicenter phase 1b study. Target Oncol 2015; 10(1): 111-23.
[http://dx.doi.org/10.1007/s11523-014-0320-2] [PMID: 24928772]
[50]
Sandhu SK, Papadopoulos K, Fong PC, et al. A first-in-human, first-in-class, phase I study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 in patients with solid tumors. Cancer Chemother Pharmacol 2013; 71(4): 1041-50.
[http://dx.doi.org/10.1007/s00280-013-2099-8] [PMID: 23385782]
[51]
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.
[http://dx.doi.org/10.1016/j.ccr.2013.01.008] [PMID: 23410977]
[52]
Nywening TM, Wang-Gillam A, Sanford DE, et al. Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial. Lancet Oncol 2016; 17(5): 651-62.
[http://dx.doi.org/10.1016/S1470-2045(16)00078-4] [PMID: 27055731]
[53]
Ahn GO, Tseng D, Liao CH, Dorie MJ, Czechowicz A, Brown JM. Inhibition of Mac-1 (CD11b/CD18) enhances tumor response to radiation by reducing myeloid cell recruitment. Proc Natl Acad Sci USA 2010; 107(18): 8363-8.
[http://dx.doi.org/10.1073/pnas.0911378107] [PMID: 20404138]
[54]
Pyonteck SM, Gadea BB, Wang HW, et al. Deficiency of the macrophage growth factor CSF-1 disrupts pancreatic neuroendocrine tumor development. Oncogene 2012; 31(11): 1459-67.
[http://dx.doi.org/10.1038/onc.2011.337] [PMID: 21822305]
[55]
Allavena P, Signorelli M, Chieppa M, et al. Anti-inflammatory properties of the novel antitumor agent yondelis (trabectedin): inhibition of macrophage differentiation and cytokine production. Cancer Res 2005; 65(7): 2964-71.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-4037] [PMID: 15805300]
[56]
Liu X, Kwon H, Li Z, Fu YX. Is CD47 an innate immune checkpoint for tumor evasion? J Hematol Oncol 2017; 10(1): 12.
[http://dx.doi.org/10.1186/s13045-016-0381-z] [PMID: 28077173]
[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): 10592-603.
[http://dx.doi.org/10.18632/oncotarget.3547] [PMID: 25871392]
[58]
Zanganeh S, Hutter G, Spitler R, et al. Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues. Nat Nanotechnol 2016; 11(11): 986-94.
[http://dx.doi.org/10.1038/nnano.2016.168] [PMID: 27668795]
[59]
Song M, Liu T, Shi C, Zhang X, Chen X. Bioconjugated Manganese Dioxide Nanoparticles Enhance Chemotherapy Response by Priming Tumor-Associated Macrophages toward M1-like Phenotype and Attenuating Tumor Hypoxia. ACS Nano 2016; 10(1): 633-47.
[http://dx.doi.org/10.1021/acsnano.5b06779] [PMID: 26650065]
[60]
Seya T, Shime H, Matsumoto M. TAMable tumor-associated macrophages in response to innate RNA sensing. OncoImmunology 2012; 1(6): 1000-1.
[http://dx.doi.org/10.4161/onci.19894] [PMID: 23162785]
[61]
Hussain SF, Kong LY, Jordan J, et al. A novel small molecule inhibitor of signal transducers and activators of transcription 3 reverses immune tolerance in malignant glioma patients. Cancer Res 2007; 67(20): 9630-6.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-1243] [PMID: 17942891]
[62]
Feng XQ, Rong LW, Wang RX, et al. Luteolin and sorafenib combination kills human hepatocellular carcinoma cells through apoptosis potentiation and JNK activation. Oncol Lett 2018; 16(1): 648-53.
[http://dx.doi.org/10.3892/ol.2018.8640] [PMID: 29928452]
[63]
Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell 2010; 141(1): 39-51.
[http://dx.doi.org/10.1016/j.cell.2010.03.014] [PMID: 20371344]
[64]
Li C, Liu B, Dai Z, Tao Y. Knockdown of VEGF receptor-1 (VEGFR-1) impairs macrophage infiltration, angiogenesis and growth of clear cell renal cell carcinoma (CRCC). Cancer Biol Ther 2011; 12(10): 872-80.
[http://dx.doi.org/10.4161/cbt.12.10.17672] [PMID: 21989163]
[65]
Santoni M, Massari F, Amantini C, et al. Emerging role of tumor associated macrophages as therapeutic targets in patients with metastatic renal cell carcinoma Cancer lmmunol Immunother 2013; 62(12): 1757-68.
[http://dx.doi.org/10.1007/s00262-013-1487-6]
[66]
Topalian SL, Drake CG, Pardoll DM. Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol 2012; 24(2): 207-12.
[http://dx.doi.org/10.1016/j.coi.2011.12.009] [PMID: 22236695]
[67]
Homet Moreno B, Ribas A. Anti-programmed cell death protein-1/ligand-1 therapy in different cancers. Br J Cancer 2015; 112(9): 1421-7.
[http://dx.doi.org/10.1038/bjc.2015.124] [PMID: 25856776]
[68]
Daurkin I, Eruslanov E, Stoffs T, et al. Tumor-associated macrophages mediate immunosuppression in the renal cancer microenvironment by activating the 15-lipoxygenase-2 pathway. Cancer Res 2011; 71(20): 6400-9.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-1261] [PMID: 21900394]
[69]
Eruslanov E, Stoffs T, Kim WJ, et al. Expansion of CCR8(+) inflammatory myeloid cells in cancer patients with urothelial and renal carcinomas. Clin Cancer Res 2013; 19(7): 1670-80.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-2091] [PMID: 23363815]
[70]
Lee JH, Lee GT, Woo SH, et al. BMP-6 in renal cell carcinoma promotes tumor proliferation through IL-10-dependent M2 polarization of tumor-associated macrophages. Cancer Res 2013; 73(12): 3604-14.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-4563] [PMID: 23633487]
[71]
Dannenmann SR, Thielicke J, Stöckli M, et al. Tumor-associated macrophages subvert T-cell function and correlate with reduced survival in clear cell renal cell carcinoma. OncoImmunology 2013; 2(3)e23562
[http://dx.doi.org/10.4161/onci.23562] [PMID: 23687622]
[72]
Komohara Y, Hasita H, Ohnishi K, et al. Macrophage infiltration and its prognostic relevance in clear cell renal cell carcinoma. Cancer Sci 2011; 102(7): 1424-31.
[http://dx.doi.org/10.1111/j.1349-7006.2011.01945.x] [PMID: 21453387]
[73]
Xu L, Zhu Y, Chen L, et al. Prognostic value of diametrically polarized tumor-associated macrophages in renal cell carcinoma. Ann Surg Oncol 2014; 21(9): 3142-50.
[http://dx.doi.org/10.1245/s10434-014-3601-1] [PMID: 24615178]
[74]
Behnes CL, Bremmer F, Hemmerlein B, Strauss A, Ströbel P, Radzun HJ. Tumor-associated macrophages are involved in tumor progression in papillary renal cell carcinoma. Virchows Arch 2014; 464(2): 191-6.
[http://dx.doi.org/10.1007/s00428-013-1523-0] [PMID: 24327306]
[75]
Boström AK, Möller C, Nilsson E, Elfving P, Axelson H, Johansson ME. Sarcomatoid conversion of clear cell renal cell carcinoma in relation to epithelial-to-mesenchymal transition. Hum Pathol 2012; 43(5): 708-19.
[http://dx.doi.org/10.1016/j.humpath.2011.06.019] [PMID: 21992819]
[76]
Sjölund J, Boström AK, Lindgren D, et al. The notch and TGF-β signaling pathways contribute to the aggressiveness of clear cell renal cell carcinoma. PLoS One 2011; 6(8)e23057
[http://dx.doi.org/10.1371/journal.pone.0023057] [PMID: 21826227]
[77]
Ho MY, Tang SJ, Chuang MJ, et al. TNF-α induces epithelial-mesenchymal transition of renal cell carcinoma cells via a GSK3β-dependent mechanism. Mol Cancer Res 2012; 10(8): 1109-19.
[http://dx.doi.org/10.1158/1541-7786.MCR-12-0160] [PMID: 22707636]
[78]
Petrella BL, Vincenti MP. Interleukin-1β mediates metalloproteinase-dependent renal cell carcinoma tumor cell invasion through the activation of CCAAT enhancer binding protein β. Cancer Med 2012; 1(1): 17-27.
[http://dx.doi.org/10.1002/cam4.7] [PMID: 23342250]
[79]
Santoni M, Massari F, Amantini C, et al. Emerging role of tumor-associated macrophages as therapeutic targets in patients with metastatic renal cell carcinoma. Cancer Immunol Immunother 2013; 62(12): 1757-68.
[http://dx.doi.org/10.1007/s00262-013-1487-6] [PMID: 24132754]
[80]
Ma C, Komohara Y, Ohnishi K, et al. Infiltration of tumor-associated macrophages is involved in CD44 expression in clear cell renal cell carcinoma. Cancer Sci 2016; 107(5): 700-7.
[http://dx.doi.org/10.1111/cas.12917] [PMID: 26918621]
[81]
Yang Z, Xie H, He D, Li L. Infiltrating macrophages increase RCC epithelial mesenchymal transition (EMT) and stem cell-like populations via AKT and mTOR signaling. Oncotarget 2016; 7(28): 44478-91.
[http://dx.doi.org/10.18632/oncotarget.9873] [PMID: 27283897]
[82]
Komohara Y, Morita T, Annan DA, et al. The Coordinated Actions of TIM-3 on Cancer and Myeloid Cells in the Regulation of Tumorigenicity and Clinical Prognosis in Clear Cell Renal Cell Carcinomas. Cancer Immunol Res 2015; 3(9): 999-1007.
[http://dx.doi.org/10.1158/2326-6066.CIR-14-0156] [PMID: 25783986]
[83]
Belgiovine C, D’Incalci M, Allavena P, Frapolli R. Tumor-associated macrophages and anti-tumor therapies: complex links. Cell Mol Life Sci 2016; 73(13): 2411-24.
[http://dx.doi.org/10.1007/s00018-016-2166-5] [PMID: 26956893]
[84]
Gül N, van Egmond M. Antibody-Dependent Phagocytosis of Tumor Cells by Macrophages: A Potent Effector Mechanism of Monoclonal Antibody Therapy of Cancer. Cancer Res 2015; 75(23): 5008-13.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-1330] [PMID: 26573795]


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VOLUME: 15
ISSUE: 7
Year: 2020
Published on: 14 October, 2020
Page: [588 - 596]
Pages: 9
DOI: 10.2174/1574888X15666200225093210
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