Cancer stem cells and tumor-associated macrophages: A roadmap for multitargeting strategies

Oncogene

Volumn 35, Issue 6, 2016, Pages 671-682

  Raggi, C ^a   Mousa, H S ^a   Correnti, M ^a   Sica, A ^a,b   Invernizzi, P ^a  

^a HUMANITAS CLINICAL AND RESEARCH CENTER   (Italy)

^b UNIVERSITY OF EASTERN PIEDMONT   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATED LEUKOCYTE CELL ADHESION MOLECULE; ALDEHYDE DEHYDROGENASE; BETA CATENIN; BLOOD CLOTTING FACTOR 8 CONCENTRATE; BREAST CANCER RESISTANCE PROTEIN; CD133 ANTIGEN; CD24 ANTIGEN; CD34 ANTIGEN; CELL SURFACE MARKER; EPHRIN RECEPTOR A4; EPIDERMAL GROWTH FACTOR RECEPTOR; HERMES ANTIGEN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 6; KRUPPEL LIKE FACTOR 4; LACTADHERIN; SONIC HEDGEHOG PROTEIN; STAT3 PROTEIN; STEM CELL FACTOR RECEPTOR; THY 1 ANTIGEN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR SOX2; VITRONECTIN RECEPTOR; WNT PROTEIN;

ACUTE MYELOBLASTIC LEUKEMIA; BREAST CANCER; CANCER STEM CELL; CELL DIFFERENTIATION; CELL STRUCTURE; COLORECTAL CANCER; EPITHELIAL MESENCHYMAL TRANSITION; GLIOBLASTOMA; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; LIVER CELL CARCINOMA; LUNG CANCER; MACROPHAGE ACTIVATION; MOLECULARLY TARGETED THERAPY; ONCOGENE C MYC; PANCREAS ADENOCARCINOMA; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; STEM CELL SELF-RENEWAL; T LYMPHOCYTE; TUMOR ASSOCIATED LEUKOCYTE; TUMOR MICROENVIRONMENT; TUMOR MODEL; VIRUS ONCOGENE; ANIMAL; GENETICS; IMMUNOLOGY; MACROPHAGE; METABOLISM; NEOPLASMS; PATHOLOGY; PHYSIOLOGY; PROCEDURES; STEM CELL NICHE; TRENDS;

ANIMALS; HUMANS; MACROPHAGES; MOLECULAR TARGETED THERAPY; NEOPLASMS; NEOPLASTIC STEM CELLS; STEM CELL NICHE; TUMOR MICROENVIRONMENT;

EID: 84958057302     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2015.132     Document Type: Review

References (181)

1. Fidler IJ, Hart IR. Biological diversity in metastatic neoplasms: origins and implications. Science 1982; 217: 998-1003.
2. Heppner GH, Miller BE. Tumor heterogeneity: biological implications and therapeutic consequences. Cancer Metastasis Rev 1983; 2: 5-23.
3. Kreso A, Dick JE. Evolution of the cancer stem cell model. Cell Stem Cell 2014; 14: 275-291.
4. Morrison SJ, Kimble J. Asymmetric and symmetric stem-cell divisions in development and cancer. Nature 2006; 441: 1068-1074.
5. Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL et al. Cancer stem cells-perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 2006; 66: 9339-9344.
6. Beachy PA, Karhadkar SS, Berman DM. Tissue repair and stem cell renewal in carcinogenesis. Nature 2004; 432: 324-331.
7. Virchow R. An address on the value of pathological experiments. Br Med J 1881; 2: 198-203.
8. Rais Y, Zviran A, Geula S, Gafni O, Chomsky E, Viukov S et al. Deterministic direct reprogramming of somatic cells to pluripotency. Nature 2013; 502: 65-70.
9. Chaffer CL, Brueckmann I, Scheel C, Kaestli AJ, Wiggins PA, Rodrigues LO et al. Normal and neoplastic nonstem cells can spontaneously convert to a stemlike state. Proc Natl Acad Sci USA 2011; 108: 7950-7955.
10. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 663-676.
11. Schoenhals M, Kassambara A, De Vos J, Hose D, Moreaux J, Klein B. Embryonic stem cell markers expression in cancers. Biochem Biophys Res Commun 2009; 383: 157-162.
12. Jeter CR, Badeaux M, Choy G, Chandra D, Patrawala L, Liu C et al. Functional evidence that the self-renewal gene NANOG regulates human tumor development. Stem Cells. 2009; 27: 993-1005.
13. Segal E, Friedman N, Koller D, Regev A. A module map showing conditional activity of expression modules in cancer. Nat Genet 2004; 36: 1090-1098.
14. Wong DJ, Liu H, Ridky TW, Cassarino D, Segal E, Chang HY. Module map of stem cell genes guides creation of epithelial cancer stem cells. Cell Stem Cell 2008; 2: 333-344.
15. Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW, Regev A et al. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet 2008; 40: 499-507.
16. Wellner U, Schubert J, Burk UC, Schmalhofer O, Zhu F, Sonntag A et al. The EMTactivator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat Cell Biol 2009; 11: 1487-1495.
17. Kong D, Banerjee S, Ahmad A, Li Y, Wang Z, Sethi S et al. Epithelial to mesenchymal transition is mechanistically linked with stem cell signatures in prostate cancer cells. PLoS One 2010; 5: e12445.
18. Morel AP, Lievre M, Thomas C, Hinkal G, Ansieau S, Puisieux A. Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS One 2008; 3: e2888.
19. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY et al. The epithelialmesenchymal transition generates cells with properties of stem cells. Cell 2008; 133: 704-715.
20. Ahmed N, Maines-Bandiera S, Quinn MA, Unger WG, Dedhar S, Auersperg N. Molecular pathways regulating EGF-induced epithelio-mesenchymal transition in human ovarian surface epithelium. Am J Physiol Cell Physiol 2006; 290: C1532-C1542.
21. Lim J, Thiery JP. Epithelial-mesenchymal transitions: insights from development. Development 2012; 139: 3471-3486.
22. Borovski T, De Sousa EMF, Vermeulen L, Medema JP. Cancer stem cell niche: the place to be. Cancer Res 2011; 71: 634-639.
23. Shigdar S, Lin J, Li Y, Yang CJ, Wei M, Zhus Y et al. Cancer stem cell targeting: the next generation of cancer therapy and molecular imaging. Ther Deliv 2012; 3: 227-244.
24. LaBarge MA. The difficulty of targeting cancer stem cell niches. Clin Cancer Res 2010; 16: 3121-3129.
25. Hollier BG, Evans K, Mani SA. The epithelial-to-mesenchymal transition and cancer stem cells: a coalition against cancer therapies. J Mammary Gland Biol Neoplasia 2009; 14: 29-43.
26. Biddle A, Mackenzie IC. Cancer stem cells and EMT in carcinoma. Cancer Metastasis Rev 2012; 31: 285-293.
27. Bromberg J. Stat proteins and oncogenesis. J Clin Invest 2002; 109: 1139-1142.
28. Zushi S, Shinomura Y, Kiyohara T, Miyazaki Y, Kondo S, Sugimachi M et al. STAT3 mediates the survival signal in oncogenic ras-transfected intestinal epithelial cells. Int J Cancer 1998; 78: 326-330.
29. Sikora A, Grzesiuk E. Heat shock response in gastrointestinal tract. J Physiol Pharmacol 2007; 58: 43-62.
30. Niu G, Wright KL, Huang M, Song L, Haura E, Turkson J et al. Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis. Oncogene 2002; 21: 2000-2008.
31. Pawlus MR, Wang L, Murakami A, Dai G, Hu CJ. STAT3 or USF2 contributes to HIF target gene specificity. PLoS One 2013; 8: e72358.
32. Zhou B, Damrauer JS, Bailey ST, Hadzic T, Jeong Y, Clark K et al. Erythropoietin promotes breast tumorigenesis through tumor-initiating cell self-renewal. J Clin Invest 2014; 124: 553-563.
33. Cook AM, Li L, Ho Y, Lin A, Stein A, Forman S et al. Role of altered growth factor receptor-mediated JAK2 signaling in growth and maintenance of human acute myeloid leukemia stem cells. Blood 2014; 123: 2826-2837.
34. Sherry MM, Reeves A, Wu JK, Cochran BH. STAT3 is required for proliferation and maintenance of multipotency in glioblastoma stem cells. Stem Cells 2009; 27: 2383-2392.
35. Liu RY, Zeng Y, Lei Z, Wang L, Yang H, Liu Z et al. JAK/STAT3 signaling is required for TGF-beta-induced epithelial-mesenchymal transition in lung cancer cells. Int J Oncol 2014; 44: 1643-1651.
36. Rokavec M, Oner MG, Li H, Jackstadt R, Jiang L, Lodygin D et al. IL-6R/STAT3/miR-34a feedback loop promotes EMT-mediated colorectal cancer invasion and metastasis. J Clin Invest 2014; 124: 1853-1867.
37. Nusse R, van Ooyen A, Cox D, Fung YK, Varmus H. Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15. Nature 1984; 307: 131-136.
38. Bienz M. beta-Catenin: a pivot between cell adhesion and Wnt signalling. Curr Biol 2005; 15: R64-R67.
39. Brembeck FH, Schwarz-Romond T, Bakkers J, Wilhelm S, Hammerschmidt M, Birchmeier W. Essential role of BCL9-2 in the switch between beta-catenin's adhesive and transcriptional functions. Genes Dev 2004; 18: 2225-2230.
40. Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science 1999; 284: 770-776.
41. Farnie G, Clarke RB. Mammary stem cells and breast cancer-role of Notch signalling. Stem Cell Rev 2007; 3: 169-175.
42. Abel EV, Kim EJ, Wu J, Hynes M, Bednar F, Proctor E et al. The Notch pathway is important in maintaining the cancer stem cell population in pancreatic cancer. PLoS One 2014; 9: e91983.
43. Abbas T, Dutta A. p21 in cancer: intricate networks and multiple activities. Nat Rev Cancer 2009; 9: 400-414.
44. Hassan KA, Wang L, Korkaya H, Chen G, Maillard I, Beer DG et al. Notch pathway activity identifies cells with cancer stem cell-like properties and correlates with worse survival in lung adenocarcinoma. Clin Cancer Res 2013; 19: 1972-1980.
45. Ninov N, Borius M, Stainier DY. Different levels of Notch signaling regulate quiescence, renewal and differentiation in pancreatic endocrine progenitors. Development 2012; 139: 1557-1567.
46. Thayer SP, di Magliano MP, Heiser PW, Nielsen CM, Roberts DJ, Lauwers GY et al. Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature 2003; 425: 851-856.
47. Liao X, Siu MK, Au CW, Wong ES, Chan HY, Ip PP et al. Aberrant activation of hedgehog signaling pathway in ovarian cancers: effect on prognosis, cell invasion and differentiation. Carcinogenesis 2009; 30: 131-140.
48. Zhao C, Chen A, Jamieson CH, Fereshteh M, Abrahamsson A, Blum J et al. Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia. Nature 2009; 458: 776-779.
49. Feldmann G, Dhara S, Fendrich V, Bedja D, Beaty R, Mullendore M et al. Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combination therapy in solid cancers. Cancer Res 2007; 67: 2187-2196.
50. Song Z, Yue W, Wei B, Wang N, Li T, Guan L et al. Sonic hedgehog pathway is essential for maintenance of cancer stem-like cells in human gastric cancer. PLoS One 2011; 6: e17687.
51. Abe Y, Oda-Sato E, Tobiume K, Kawauchi K, Taya Y, Okamoto K et al. Hedgehog signaling overrides p53-mediated tumor suppression by activating Mdm2. Proc Natl Acad Sci USA 2008; 105: 4838-4843.
52. Li SH, Fu J, Watkins DN, Srivastava RK, Shankar S. Sulforaphane regulates selfrenewal of pancreatic cancer stem cells through the modulation of Sonic hedgehog-GLI pathway. Mol Cell Biochemi 2013; 373: 217-227.
53. Lu H, Ouyang W, Huang C. Inflammation, a key event in cancer development. Mol Cancer Res 2006; 4: 221-233.
54. Hirsch HA, Iliopoulos D, Struhl K. Metformin inhibits the inflammatory response associated with cellular transformation and cancer stem cell growth. Proc Natl Acad Sci USA. 2013; 110: 972-977.
55. Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR et al. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 2006; 366: 2-16.
56. Normanno N, Bianco C, De Luca A, Salomon DS. The role of EGF-related peptides in tumor growth. Front Biosci 2001; 6: D685-D707.
57. Salomon DS, Brandt R, Ciardiello F, Normanno N. Epidermal growth factorrelated peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 1995; 19: 183-232.
58. Salomon DS, Kim N, Saeki T, Ciardiello F. Transforming growth factor-alpha: an oncodevelopmental growth factor. Cancer Cells 1990; 2: 389-397.
59. Marmor MD, Yarden Y. Role of protein ubiquitylation in regulating endocytosis of receptor tyrosine kinases. Oncogene 2004; 23: 2057-2070.
60. Jorissen RN, Walker F, Pouliot N, Garrett TP, Ward CW, Burgess AW. Epidermal growth factor receptor: mechanisms of activation and signalling. Exp Cell Res 2003; 284: 31-53.
61. Arasada RR, Amann JM, Rahman MA, Huppert SS, Carbone DP. EGFR blockade enriches for lung cancer stem-like cells through Notch3-dependent signaling. Cancer Res 2014; 74: 5572-5584.
62. Junttila MR, de Sauvage FJ. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature 2013; 501: 346-354.
63. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010; 140: 883-899.
64. Korkaya H, Liu S, Wicha MS. Breast cancer stem cells, cytokine networks, and the tumor microenvironment. J Clin Invest 2011; 121: 3804-3809.
65. Raggi C, Invernizzi P, Andersen JB. Impact of microenvironment and stem-like plasticity in cholangiocarcinoma: molecular networks and biological concepts. J Hepatol 2015; 62: 198-207.
66. Moore KA, Lemischka IR. Stem cells and their niches. Science 2006; 311: 1880-1885.
67. Margol A, Robison N, Gnanachandran J, Hung LT, Kennedy R, Vali M et al. Tumor associated macrophages in SHH subgroup of medulloblastomas. Clin Cancer Res 2014; 21: 1457-1465.
68. Noy R, Pollard JW. Tumor-associated macrophages: from mechanisms to therapy. Immunity 2014; 41: 49-61.
69. Mantovani A. The yin-yang of tumor-associated neutrophils. Cancer Cell 2009; 16: 173-174.
70. Mantovani A, Allavena P, Sica A. Tumour-associated macrophages as a prototypic type II polarised phagocyte population: role in tumour progression. Eur J Cancer 2004; 40: 1660-1667.
71. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008; 454: 436-444.
72. Mantovani A, Biswas SK, Galdiero MR, Sica A, Locati M. Macrophage plasticity and polarization in tissue repair and remodelling. J Pathol 2013; 229: 176-185.
73. Coussens LM, Zitvogel L, Palucka AK. Neutralizing tumor-promoting chronic inflammation: a magic bullet? Science 2013; 339: 286-291.
74. Wilson E, Leszczynska K, Poulter NS, Edelmann F, Salisbury VA, Noy PJ et al. RhoJ interacts with the GIT-PIX complex and regulates focal adhesion disassembly. J Cell Sci 2014; 127: 3039-3051.
75. Movahedi K, Laoui D, Gysemans C, Baeten M, Stange G, Van den Bossche J et al. Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes. Cancer Res 2010; 70: 5728-5739.
76. Lewis CE, Pollard JW. Distinct role of macrophages in different tumor microenvironments. Cancer Res 2006; 66: 605-612.
77. Biswas SK, Allavena P, Mantovani A. Tumor-associated macrophages: functional diversity, clinical significance, and open questions. Semin Immunopathol 2013; 35: 585-600.
78. Richards DM, Hettinger J, Feuerer M. Monocytes and macrophages in cancer: development and functions. Cancer Microenviron 2013; 6: 179-191.
79. Galdiero MR, Bonavita E, Barajon I, Garlanda C, Mantovani A, Jaillon S. Tumor associated macrophages and neutrophils in cancer. Immunobiology 2013; 218: 1402-1410.
80. Laoui D, Van Overmeire E, Di Conza G, Aldeni C, Keirsse J, Morias Y et al. Tumor hypoxia does not drive differentiation of tumor-associated macrophages but rather fine-tunes the M2-like macrophage population. Cancer Res 2014; 74: 24-30.
81. Allavena P, Sica A, Solinas G, Porta C, Mantovani A. The inflammatory microenvironment in tumor progression: the role of tumor-associated macrophages. Crit Rev Oncol Hematol 2008; 66: 1-9.
82. Siveen KS, Kuttan G. Role of macrophages in tumour progression. Immunol Lett 2009; 123: 97-102.
83. Eljaszewicz A, Wiese M, Helmin-Basa A, Jankowski M, Gackowska L, Kubiszewska I et al. Collaborating with the enemy: function of macrophages in the development of neoplastic disease. Mediators Inflamm 2013; 2013: 831387.
84. Riether C, Schurch CM, Ochsenbein AF. Regulation of hematopoietic and leukemic stem cells by the immune system. Cell Death Differ 2014; 22: 187-198.
85. Pollard JW. Trophic macrophages in development and disease. Nat Rev Immunol 2009; 9: 259-270.
86. Gyorki DE, Asselin-Labat ML, van Rooijen N, Lindeman GJ, Visvader JE. Resident macrophages influence stem cell activity in the mammary gland. Breast Cancer Res 2009; 11: R62.
87. London A, Itskovich E, Benhar I, Kalchenko V, Mack M, Jung S et al. Neuroprotection and progenitor cell renewal in the injured adult murine retina requires healing monocyte-derived macrophages. J Exp Med 2011; 208: 23-39.
88. Kim J, Hematti P. Mesenchymal stem cell-educated macrophages: a novel type of alternatively activated macrophages. Exp Hemat 2009; 37: 1445-1453.
89. Asimakopoulos F, Kim J, Denu RA, Hope C, Jensen JL, Ollar SJ et al. Macrophages in multiple myeloma: emerging concepts and therapeutic implications. Leuk Lymphoma 2013; 54: 2112-2121.
90. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 1997; 3: 730-737.
91. Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 1994; 367: 645-648.
92. Bradstock KF, Gottlieb DJ. Interaction of acute leukemia cells with the bone marrow microenvironment: implications for control of minimal residual disease. Leuk Lymph 1995; 18: 1-16.
93. Ishikawa F, Yoshida S, Saito Y, Hijikata A, Kitamura H, Tanaka S et al. Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region. Nat Biotechnol 2007; 25: 1315-1321.
94. Bhatia R, McGlave PB, Dewald GW, Blazar BR, Verfaillie CM. Abnormal function of the bone marrow microenvironment in chronic myelogenous leukemia: role of malignant stromal macrophages. Blood 1995; 85: 3636-3645.
95. Winkler IG, Sims NA, Pettit AR, Barbier V, Nowlan B, Helwani F et al. Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs. Blood 2010; 116: 4815-4828.
96. Chow A, Lucas D, Hidalgo A, Mendez-Ferrer S, Hashimoto D, Scheiermann C et al. Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche. J Exp Med 2011; 208: 261-271.
97. Chow A, Huggins M, Ahmed J, Hashimoto D, Lucas D, Kunisaki Y et al. CD169(+) macrophages provide a niche promoting erythropoiesis under homeostasis and stress. Nat Med 2013; 19: 429-436.
98. Ludin A, Itkin T, Gur-Cohen S, Mildner A, Shezen E, Golan K et al. Monocytes-macrophages that express alpha-smooth muscle actin preserve primitive hematopoietic cells in the bone marrow. Nat Immunol 2012; 13: 1072-1082.
99. Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med 2006; 12: 1167-1174.
100. Tavor S, Petit I, Porozov S, Avigdor A, Dar A, Leider-Trejo L et al. CXCR4 regulates migration and development of human acute myelogenous leukemia stem cells in transplanted NOD/SCID mice. Cancer Res 2004; 64: 2817-2824.
101. Jaiswal S, Jamieson CH, Pang WW, Park CY, Chao MP, Majeti R et al. CD47 is upregulated on circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis. Cell 2009; 138: 271-285.
102. Majeti R, Chao MP, Alizadeh AA, Pang WW, Jaiswal S, Gibbs Jr KD et al. CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell 2009; 138: 286-299.
103. Theocharides AP, Jin L, Cheng PY, Prasolava TK, Malko AV, Ho JM et al. Disruption of SIRPalpha signaling in macrophages eliminates human acute myeloid leukemia stem cells in xenografts. J Exp Med 2012; 209: 1883-1899.
104. Tseng D, Volkmer JP, Willingham SB, Contreras-Trujillo H, Fathman JW, Fernhoff NB et al. Anti-CD47 antibody-mediated phagocytosis of cancer by macrophages primes an effective antitumor T-cell response. Proc Natl Acad Sci USA. 2013; 110: 11103-11108.
105. Liu DQ, Li LM, Guo YL, Bai R, Wang C, Bian Z et al. Signal regulatory protein alpha negatively regulates beta2 integrin-mediated monocyte adhesion, transendothelial migration and phagocytosis. PLoS One 2008; 3: e3291.
106. van Beek EM, Cochrane F, Barclay AN, van den Berg TK. Signal regulatory proteins in the immune system. J Immunol 2005; 175: 7781-7787.
107. Smith RE, Patel V, Seatter SD, Deehan MR, Brown MH, Brooke GP et al. A novel MyD-1 (SIRP-1alpha) signaling pathway that inhibits LPS-induced TNFalpha production by monocytes. Blood 2003; 102: 2532-2540.
108. Zhao XW, van Beek EM, Schornagel K, Van der Maaden H, Van Houdt M, Otten MA et al. CD47-signal regulatory protein-alpha (SIRPalpha) interactions form a barrier for antibody-mediated tumor cell destruction. Proc Natl Acad Sci USA 2011; 108: 18342-18347.
109. Kaur S, Soto-Pantoja DR, Stein EV, Liu C, Elkahloun AG, Pendrak ML et al. Thrombospondin-1 signaling through CD47 inhibits self-renewal by regulating c-Myc and other stem cell transcription factors. Sci Rep 2013; 3: 1673.
110. Nie Z, Hu G, Wei G, Cui K, Yamane A, Resch W et al. c-Myc is a universal amplifier of expressed genes in lymphocytes and embryonic stem cells. Cell 2012; 151: 68-79.
111. Zhang Y, Sime W, Juhas M, Sjolander A. Crosstalk between colon cancer cells and macrophages via inflammatory mediators and CD47 promotes tumour cell migration. Eur J Cancer 2013; 49: 3320-3334.
112. Monney L, Sabatos CA, Gaglia JL, Ryu A, Waldner H, Chernova T et al. Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature 2002; 415: 536-541.
113. Zhang Y, Ma CJ, Wang JM, Ji XJ, Wu XY, Jia ZS et al. Tim-3 negatively regulates IL-12 expression by monocytes in HCV infection. PLoS One 2011; 6: e19664.
114. Kryczek I, Zou L, Rodriguez P, Zhu G, Wei S, Mottram P et al. B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J Exp Med 2006; 203: 871-881.
115. Jan M, Chao MP, Cha AC, Alizadeh AA, Gentles AJ, Weissman IL et al. Prospective separation of normal and leukemic stem cells based on differential expression of TIM3, a human acute myeloid leukemia stem cell marker. Proc Natl Acad Sci USA 2011; 108: 5009-5014.
116. Kikushige Y, Shima T, Takayanagi S, Urata S, Miyamoto T, Iwasaki H et al. TIM-3 is a promising target to selectively kill acute myeloid leukemia stem cells. Cell Stem Cell 2010; 7: 708-717.
117. Gao L, Yu S, Zhang X. Hypothesis: Tim-3/Galectin-9, a new pathway for leukemia stem cells survival by promoting expansion of myeloid-derived suppressor cells and differentiating into tumor-associated macrophages. Cell Biochem Biophys 2014; 70: 273-277.
118. Fourcade J, Sun Z, Benallaoua M, Guillaume P, Luescher IF, Sander C et al. Upregulation of Tim-3 and PD-1 expression is associated with tumor antigenspecific CD8+ T cell dysfunction in melanoma patients. J Exp Med 2010; 207: 2175-2186.
119. Gao X, Zhu Y, Li G, Huang H, Zhang G, Wang F et al. TIM-3 expression characterizes regulatory T cells in tumor tissues and is associated with lung cancer progression. PLoS One 2012; 7: e30676.
120. Wu J, Liu C, Qian S, Hou H. The expression of Tim-3 in peripheral blood of ovarian cancer. DNA Cell Biol 2013; 32: 648-653.
121. Shang Y, Li Z, Li H, Xia H, Lin Z. TIM-3 expression in human osteosarcoma: correlation with the expression of epithelial-mesenchymal transition-specific biomarkers. Oncol Lett 2013; 6: 490-494.
122. Ngiow SF, von Scheidt B, Akiba H, Yagita H, Teng MW, Smyth MJ. Anti-TIM3 antibody promotes T cell IFN-gamma-mediated antitumor immunity and suppresses established tumors. Cancer Res 2011; 71: 3540-3551.
123. Ezekowitz RA. Local opsonization for apoptosis? Nat Immunol 2002; 3: 510-512.
124. Hanayama R, Tanaka M, Miwa K, Shinohara A, Iwamatsu A, Nagata S. Identification of a factor that links apoptotic cells to phagocytes. Nature 2002; 417: 182-187.
125. Jinushi M, Chiba S, Yoshiyama H, Masutomi K, Kinoshita I, Dosaka-Akita H et al. Tumor-associated macrophages regulate tumorigenicity and anticancer drug responses of cancer stem/initiating cells. Proc Natl Acad Sci USA 2011; 108: 12425-12430.
126. Brissette MJ, Lepage S, Lamonde AS, Sirois I, Groleau J, Laurin LP et al. MFG-E8 released by apoptotic endothelial cells triggers anti-inflammatory macrophage reprogramming. PLoS One 2012; 7: e36368.
127. Segall JE, Tyerech S, Boselli L, Masseling S, Helft J, Chan A et al. EGF stimulates lamellipod extension in metastatic mammary adenocarcinoma cells by an actindependent mechanism. Clin Exp Metastasis 1996; 14: 61-72.
128. Lu Z, Ghosh S, Wang Z, Hunter T. Downregulation of caveolin-1 function by EGF leads to the loss of E-cadherin, increased transcriptional activity of beta-catenin, and enhanced tumor cell invasion. Cancer Cell 2003; 4: 499-515.
129. O'Sullivan C, Lewis CE, Harris AL, McGee JO. Secretion of epidermal growth factor by macrophages associated with breast carcinoma. Lancet 1993; 342: 148-149.
130. Peoples GE, Blotnick S, Takahashi K, Freeman MR, Klagsbrun M, Eberlein TJ. T lymphocytes that infiltrate tumors and atherosclerotic plaques produce heparin-binding epidermal growth factor-like growth factor and basic fibroblast growth factor: a potential pathologic role. Proc Natl Acad Sci USA 1995; 92: 6547-6551.
131. Goswami S, Sahai E, Wyckoff JB, Cammer M, Cox D, Pixley FJ et al. Macrophages promote the invasion of breast carcinoma cells via a colonystimulating factor-1/epidermal growth factor paracrine loop. Cancer Res 2005; 65: 5278-5283.
132. Sapi E, Kacinski BM. The role of CSF-1 in normal and neoplastic breast physiology. Proc Soc Exp Biol Med 1999; 220: 1-8.
133. Yang J, Liao D, Chen C, Liu Y, Chuang TH, Xiang R et al. Tumor-associated macrophages regulate murine breast cancer stem cells through a novel paracrine EGFR/Stat3/Sox-2 signaling pathway. Stem Cells 2013; 31: 248-258.
134. Lu H, Clauser KR, Tam WL, Frose J, Ye X, Eaton EN et al. A breast cancer stem cell niche supported by juxtacrine signalling from monocytes and macrophages. Nat Cell Biol 2014; 16: 1105-1117.
135. Mitchem JB, Brennan DJ, Knolhoff BL, Belt BA, Zhu Y, Sanford DE et al. Targeting tumor-infiltrating macrophages decreases tumor-initiating cells, relieves immunosuppression, and improves chemotherapeutic responses. Cancer Res 2013; 73: 1128-1141.
136. Weizman N, Krelin Y, Shabtay-Orbach A, Amit M, Binenbaum Y, Wong RJ et al. Macrophages mediate gemcitabine resistance of pancreatic adenocarcinoma by upregulating cytidine deaminase. Oncogene 2013; 33: 3812-3819.
137. Zhou W, Ke SQ, Huang Z, Flavahan W, Fang X, Paul J et al. Periostin secreted by glioblastoma stem cells recruits M2 tumour-associated macrophages and promotes malignant growth. Nat Cell Biol 2015; 17: 170-182.
138. Wan S, Zhao E, Kryczek I, Vatan L, Sadovskaya A, Ludema G et al. Tumorassociated macrophages produce interleukin 6 and signal via STAT3 to promote expansion of human hepatocellular carcinoma stem cells. Gastroenterology 2014; 147: 1393-1404.
139. Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 2012; 122: 787-795.
140. He KF, Zhang L, Huang CF, Ma SR, Wang YF, Wang WM et al. CD163+ tumorassociated macrophages correlated with poor prognosis and cancer stem cells in oral squamous cell carcinoma. BioMed Res Int 2014; 2014: 838632.
141. Fan QM, Jing YY, Yu GF, Kou XR, Ye F, Gao L et al. Tumor-associated macrophages promote cancer stem cell-like properties via transforming growth factor-beta1-induced epithelial-mesenchymal transition in hepatocellular carcinoma. Cancer Lett 2014; 352: 160-168.
142. Yamashina T, Baghdadi M, Yoneda A, Kinoshita I, Suzu S, Dosaka-Akita H et al. Cancer stem-like cells derived from chemoresistant tumors have a unique capacity to prime tumorigenic myeloid cells. Cancer Res 2014; 74: 2698-2709.
143. Chaturvedi P, Gilkes DM, Takano N, Semenza GL. Hypoxia-inducible factordependent signaling between triple-negative breast cancer cells and mesenchymal stem cells promotes macrophage recruitment. Proc Natl Acad Sci USA 2014; 111: E2120-E2129.
144. DeNardo DG, Brennan DJ, Rexhepaj E, Ruffell B, Shiao SL, Madden SF et al. Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer Discov 2011; 1: 54-67.
145. Buiting AM, Van Rooijen N. Liposome mediated depletion of macrophages: an approach for fundamental studies. J Drug Target 1994; 2: 357-362.
146. Germano G, Frapolli R, Simone M, Tavecchio M, Erba E, Pesce S et al. Antitumor and anti-inflammatory effects of trabectedin on human myxoid liposarcoma cells. Cancer Res 2010; 70: 2235-2244.
147. Yang L, DeBusk LM, Fukuda K, Fingleton B, Green-Jarvis B, Shyr Y et al. Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell 2004; 6: 409-421.
148. Kusmartsev S, Nagaraj S, Gabrilovich DI. Tumor-associated CD8+ T cell tolerance induced by bone marrow-derived immature myeloid cells. J Immunol 2005; 175: 4583-4592.
149. Kusmartsev S, Gabrilovich DI. STAT1 signaling regulates tumor-associated macrophage-mediated T cell deletion. J Immunol 2005; 174: 4880-4891.
150. Ries CH, Cannarile MA, Hoves S, Benz J, Wartha K, Runza V et al. Targeting tumorassociated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer Cell 2014; 25: 846-859.
151. Sarkar S, Doring A, Zemp FJ, Silva C, Lun X, Wang X et al. Therapeutic activation of macrophages and microglia to suppress brain tumor-initiating cells. Nat Neurosci 2014; 17: 46-55.
152. Samanani S, Mishra M, Silva C, Verhaeghe B, Wang J, Tong J et al. Screening for inhibitors of microglia to reduce neuroinflammation. CNS Neurol Disord Drug Targets 2013; 12: 741-749.
153. Hiramatsu H, Nishikomori R, Heike T, Ito M, Kobayashi K, Katamura K et al. Complete reconstitution of human lymphocytes from cord blood CD34+ cells using the NOD/SCID/gammacnull mice model. Blood 2003; 102: 873-880.
154. Takagi S, Saito Y, Hijikata A, Tanaka S, Watanabe T, Hasegawa T et al. Membranebound human SCF/KL promotes in vivo human hematopoietic engraftment and myeloid differentiation. Blood 2012; 119: 2768-2777.
155. Su S, Liu Q, Chen J, Chen F, He C, Huang D et al. A positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis. Cancer Cell 2014; 25: 605-620.
156. Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M et al. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 2007; 1: 313-323.
157. Esch JS 2nd, Knoefel WT, Klein M, Ghodsizad A, Fuerst G, Poll LW et al. Portal application of autologous CD133+ bone marrow cells to the liver: a novel concept to support hepatic regeneration. Stem Cells 2005; 23: 463-470.
158. Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 2007; 1: 555-567.
159. Carpentino JE, Hynes MJ, Appelman HD, Zheng T, Steindler DA, Scott EW et al. Aldehyde dehydrogenase-expressing colon stem cells contribute to tumorigenesis in the transition from colitis to cancer. Cancer Res 2009; 69: 8208-8215.
160. Li X, Lewis MT, Huang J, Gutierrez C, Osborne CK, Wu MF et al. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst 2008; 100: 672-679.
161. Raggi C, Factor VM, Seo D, Holczbauer A, Gillen MC, Marquardt JU et al. Epigenetic reprogramming modulates malignant properties of human liver cancer. Hepatology 2014; 59: 2251-2262.
162. Marquardt JU, Raggi C, Andersen JB, Seo D, Avital I, Geller D et al. Human hepatic cancer stem cells are characterized by common stemness traits and diverse oncogenic pathways. Hepatology 2011; 54: 1031-1042.
163. Medema JP. Cancer stem cells: the challenges ahead. Nat Cell Biol 2013; 15: 338-344.
164. Baguley BC. Multiple drug resistance mechanisms in cancer. Mol Biotechnol 2010; 46: 308-316.
165. Zhou S, Schuetz JD, Bunting KD, Colapietro AM, Sampath J, Morris JJ et al. The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med 2001; 7: 1028-1034.
166. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T et al. Identification of human brain tumour initiating cells. Nature 2004; 432: 396-401.
167. Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D et al. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res 2005; 65: 5506-5511.
168. Li T, Su Y, Mei Y, Leng Q, Leng B, Liu Z et al. ALDH1A1 is a marker for malignant prostate stem cells and predictor of prostate cancer patients' outcome. Lab Invest 2010; 90: 234-244.
169. Chen J, Li Y, Yu TS, McKay RM, Burns DK, Kernie SG et al. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 2012; 488: 522-526.
170. Schepers AG, Snippert HJ, Stange DE, van den Born M, van Es JH, van de Wetering M et al. Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas. Science 2012; 337: 730-735.
171. Driessens G, Beck B, Caauwe A, Simons BD, Blanpain C. Defining the mode of tumour growth by clonal analysis. Nature 2012; 488: 527-530.
172. Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature 2013; 496: 445-455.
173. Korkaya H, Wicha MS. Inflammation and autophagy conspire to promote tumor growth. Cell Cycle 2011; 10: 2623-2624.
174. Porta C, Rimoldi M, Raes G, Brys L, Ghezzi P, Di Liberto D et al. Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor kappaB. Proc Natl Acad Sci USA 2009; 106: 14978-14983.
175. Porta C, Larghi P, Rimoldi M, Totaro MG, Allavena P, Mantovani A et al. Cellular and molecular pathways linking inflammation and cancer. Immunobiology 2009; 214: 761-777.
176. Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 2014; 41: 14-20.
177. Locati M, Mantovani A, Sica A. Macrophage activation and polarization as an adaptive component of innate immunity. Adv Immunol 2013; 120: 163-184.
178. Li L, Ng DS, Mah W, Almeida FF, Rahmat SA, Rao VK et al. A unique role for p53 in the regulation of M2 macrophage polarization. Cell Death Differ 2014.
179. Korkaya H, Liu S, Wicha MS. Regulation of cancer stem cells by cytokine networks: attacking cancer's inflammatory roots. Clin Cancer Res 2011; 17: 6125-6129.
180. Liu S, Ginestier C, Ou SJ, Clouthier SG, Patel SH, Monville F et al. Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks. Cancer Res 2011; 71: 614-624.
181. Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol 2008; 8: 958-969.