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Tumor Microenvironment and Cellular Stress pp 83–99Cite as

Escape Mechanisms from Antiangiogenic Therapy: An Immune Cell’s Perspective

Part of the Advances in Experimental Medicine and Biology book series (AEMB,volume 772)

Abstract

Neovascularization, the formation of new blood vessels, has become a well-established hallmark of cancer. Its functional importance for the manifestation and progression of tumors has been validated further by the beneficial therapeutic effects of angiogenesis inhibitors, most notably those targeting vascular endothelial growth factor signaling pathways. However, with the transient and short-lived nature of patient response, it has become evident that tumors have the ability to adapt to the pressures of vascular growth restriction. Observations made both in the clinic and at the bench suggest the existence of several escape mechanisms that either reestablish neovascularization in tumors or change tumor behavior to enable propagation and progression without obligate neovascularization. Some of these bypass mechanisms are regulated by low oxygen conditions (hypoxia) caused by therapy-induced vessel regression. Induction of hypoxia and hypoxia-inducible factors regulate a wide range of tumor-promoting pathways, including those of neovascularization, that can upregulate additional proangiogenic factors and drive the recruitment of various bone marrow–derived cells that have the capacity to express proangiogenic factors or directly contribute to neovasculature.

Keywords

  • Cancer
  • Antiangiogenic therapy
  • Resistance
  • Innate immune cells
  • Macrophages
  • Myeloid-derived suppressor cells (MDSCs)
  • Neovascularization

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References

  • Bates DO, Hillman NJ, Williams B, Neal CR, Pocock TM (2002) Regulation of microvascular permeability by vascular endothelial growth factors. J Anat 200:581–597

    PubMed  CrossRef  CAS  Google Scholar 

  • Bergers G, Hanahan D (2008) Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer 8:592–603

    PubMed  CrossRef  CAS  Google Scholar 

  • Bergers G, Song S (2005) The role of pericytes in blood-vessel formation and maintenance. Neuro Oncol 7:452–464

    PubMed  CrossRef  CAS  Google Scholar 

  • Bergers G, Javaherian K, Lo KM, Folkman J, Hanahan D (1999) Effects of angiogenesis inhibitors on multistage carcinogenesis in mice. Science 284:808–812

    PubMed  CrossRef  CAS  Google Scholar 

  • Blouw B, Song H, Tihan T, Bosze J, Ferrara N, Gerber HP, Johnson RS, Bergers G (2003) The hypoxic response of tumors is dependent on their microenvironment. Cancer Cell 4:133–146

    PubMed  CrossRef  CAS  Google Scholar 

  • Butler JM, Kobayashi H, Rafii S (2010) Instructive role of the vascular niche in promoting tumour growth and tissue repair by angiocrine factors. Nat Rev Cancer 10:138–146

    PubMed  CrossRef  CAS  Google Scholar 

  • Casanovas O, Hicklin DJ, Bergers G, Hanahan D (2005) Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell 8: 299–309

    PubMed  CrossRef  CAS  Google Scholar 

  • Chung AS, Lee J, Ferrara N (2010) Targeting the tumour vasculature: insights from physiological angiogenesis. Nat Rev Cancer 10:505–514

    PubMed  CrossRef  CAS  Google Scholar 

  • Cooke VG, Lebleu VS, Keskin D, Khan Z, O’Connell JT, Teng Y, Duncan MB, Xie L, Maeda G, Vong S et al (2012) Pericyte depletion results in hypoxia-associated epithelial-to-mesenchymal transition and metastasis mediated by met signaling pathway. Cancer Cell 21:66–81

    PubMed  CrossRef  CAS  Google Scholar 

  • De Palma M, Venneri MA, Galli R, Sergi Sergi L, Politi LS, Sampaolesi M, Naldini L (2005) Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell 8:211–226

    PubMed  CrossRef  Google Scholar 

  • De Palma M, Murdoch C, Venneri MA, Naldini L, Lewis CE (2007) Tie2-expressing monocytes: regulation of tumor angiogenesis and therapeutic implications. Trends Immunol 28:519–524

    PubMed  CrossRef  Google Scholar 

  • Diaz-Montero CM, Salem ML, Nishimura MI, Garrett-Mayer E, Cole DJ, Montero AJ (2009) Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother 58:49–59

    PubMed  CrossRef  CAS  Google Scholar 

  • Du R, Lu KV, Petritsch C, Liu P, Ganss R, Passegue E, Song H, Vandenberg S, Johnson RS, Werb Z et al (2008a) HIF1alpha induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell 13:206–220

    PubMed  CrossRef  CAS  Google Scholar 

  • Du R, Petritsch C, Lu K, Liu P, Haller A, Ganss R, Song H, Vandenberg S, Bergers G (2008b) Matrix metalloproteinase-2 regulates vascular patterning and growth affecting tumor cell survival and invasion in GBM. Neuro-oncology 10:254–264

    PubMed  CrossRef  CAS  Google Scholar 

  • Ebos JM, Kerbel RS (2011) Antiangiogenic therapy: impact on invasion, disease progression, and metastasis. Nat Rev Clin Oncol 8:210–221

    PubMed  CrossRef  CAS  Google Scholar 

  • Ebos JM, Lee CR, Cruz-Munoz W, Bjarnason GA, Christensen JG, Kerbel RS (2009) Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 15:232–239

    PubMed  CrossRef  CAS  Google Scholar 

  • Ferrara N (2002) VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer 2:795–803

    PubMed  CrossRef  CAS  Google Scholar 

  • Ferrara N (2004) Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 25:581–611

    PubMed  CrossRef  CAS  Google Scholar 

  • Ferrara N, Hillan KJ, Novotny W (2005) Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy. Biochem Biophys Res Commun 333:328–335

    PubMed  CrossRef  CAS  Google Scholar 

  • Filipazzi P, Valenti R, Huber V, Pilla L, Canese P, Iero M, Castelli C, Mariani L, Parmiani G, Rivoltini L (2007) Identification of a new subset of myeloid suppressor cells in peripheral blood of melanoma patients with modulation by a granulocyte-macrophage colony-stimulation factor-based antitumor vaccine. J Clin Oncol Off J Am Soc Clin Oncol 25:2546–2553

    CrossRef  CAS  Google Scholar 

  • Fischer C, Jonckx B, Mazzone M, Zacchigna S, Loges S, Pattarini L, Chorianopoulos E, Liesenborghs L, Koch M, De Mol M et al (2007) Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels. Cell 131:463–475

    PubMed  CrossRef  CAS  Google Scholar 

  • Folkman J (2007) Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov 6:273–286

    PubMed  CrossRef  CAS  Google Scholar 

  • Folkman J, Merler E, Abernathy C, Williams G (1971) Isolation of a tumor factor responsible for angiogenesis. J Exp Med 133:275–288

    PubMed  CrossRef  CAS  Google Scholar 

  • Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, Semenza GL (1996) Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol 16:4604–4613

    PubMed  CAS  Google Scholar 

  • Gao D, Nolan DJ, Mellick AS, Bambino K, McDonnell K, Mittal V (2008) Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis. Science 319:195–198

    PubMed  CrossRef  CAS  Google Scholar 

  • Gorre ME, Sawyers CL (2002) Molecular mechanisms of resistance to STI571 in chronic myeloid leukemia. Curr Opin Hematol 9:303–307

    PubMed  CrossRef  Google Scholar 

  • Greenberg JI, Shields DJ, Barillas SG, Acevedo LM, Murphy E, Huang J, Scheppke L, Stockmann C, Johnson RS, Angle N et al (2008) A role for VEGF as a negative regulator of pericyte function and vessel maturation. Nature 456:809–813

    PubMed  CrossRef  CAS  Google Scholar 

  • Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353–364

    PubMed  CrossRef  CAS  Google Scholar 

  • Hillen F, Griffioen AW (2007) Tumour vascularization: sprouting angiogenesis and beyond. Cancer Metastasis Rev 26:489–502

    PubMed  CrossRef  Google Scholar 

  • Hlushchuk R, Riesterer O, Baum O, Wood J, Gruber G, Pruschy M, Djonov V (2008) Tumor recovery by angiogenic switch from sprouting to intussusceptive angiogenesis after treatment with PTK787/ZK222584 or ionizing radiation. Am J Pathol 173:1173–1185

    PubMed  CrossRef  CAS  Google Scholar 

  • Hlushchuk R, Makanya AN, Djonov V (2011) Escape mechanisms after antiangiogenic treatment, or why are the tumors growing again? Int J Dev Biol 55:563–567

    PubMed  CrossRef  CAS  Google Scholar 

  • Jain RK (2005a) Antiangiogenic therapy for cancer: current and emerging concepts. Oncology 19:7–16

    PubMed  Google Scholar 

  • Jain RK (2005b) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307:58–62

    PubMed  CrossRef  CAS  Google Scholar 

  • Keith B, Johnson RS, Simon MC (2011) HIF1alpha and HIF2alpha: sibling rivalry in hypoxic tumour growth and progression. Nat Rev Cancer 12:9–22

    PubMed  Google Scholar 

  • Kelly BD, Hackett SF, Hirota K, Oshima Y, Cai Z, Berg-Dixon S, Rowan A, Yan Z, Campochiaro PA, Semenza GL (2003) Cell type-specific regulation of angiogenic growth factor gene expression and induction of angiogenesis in nonischemic tissue by a constitutively active form of hypoxia-inducible factor 1. Circ Res 93:1074–1081

    PubMed  CrossRef  CAS  Google Scholar 

  • Ku DD, Zaleski JK, Liu S, Brock TA (1993) Vascular endothelial growth factor induces EDRF-dependent relaxation in coronary arteries. Am J Physiol 265:H586–H592

    PubMed  CAS  Google Scholar 

  • Kuhnert F, Kirshner JR, Thurston G (2011) Dll4-Notch signaling as a therapeutic target in tumor angiogenesis. Vas Cell 3:20

    CrossRef  CAS  Google Scholar 

  • Kujawski M, Kortylewski M, Lee H, Herrmann A, Kay H, Yu H (2008) Stat3 mediates myeloid cell-dependent tumor angiogenesis in mice. J Clin Invest 118:3367–3377

    PubMed  CrossRef  CAS  Google Scholar 

  • LeCouter J, Kowalski J, Foster J, Hass P, Zhang Z, Dillard-Telm L, Frantz G, Rangell L, DeGuzman L, Keller GA et al (2001) Identification of an angiogenic mitogen selective for endocrine gland endothelium. Nature 412:877–884

    PubMed  CrossRef  CAS  Google Scholar 

  • Leek RD, Lewis CE, Whitehouse R, Greenall M, Clarke J, Harris AL (1996) Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res 56:4625–4629

    PubMed  CAS  Google Scholar 

  • Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306–1309

    PubMed  CrossRef  CAS  Google Scholar 

  • Li C, Shintani S, Terakado N, Nakashiro K, Hamakawa H (2002) Infiltration of tumor-associated macrophages in human oral squamous cell carcinoma. Oncol Rep 9:1219–1223

    PubMed  Google Scholar 

  • Lin EY, Nguyen AV, Russell RG, Pollard JW (2001) Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med 193:727–740

    PubMed  CrossRef  CAS  Google Scholar 

  • Lin EY, Li JF, Gnatovskiy L, Deng Y, Zhu L, Grzesik DA, Qian H, Xue XN, Pollard JW (2006) Macrophages regulate the angiogenic switch in a mouse model of breast cancer. Cancer Res 66:11238–11246

    PubMed  CrossRef  CAS  Google Scholar 

  • Lu KV, Chang JP, Parachoniak CA, Pandika MM, Aghi MK, Meyronet D, Isachenko N, Fouse SD, Phillips JJ, Cheresh DA et al (2012) VEGF inhibits tumor cell invasion and mesenchymal transition through a MET/VEGFR2 complex. Cancer Cell 22:21–35

    PubMed  CrossRef  CAS  Google Scholar 

  • Lyden D, Hattori K, Dias S, Costa C, Blaikie P, Butros L, Chadburn A, Heissig B, Marks W, Witte L et al (2001) Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 7:1194–1201

    PubMed  CrossRef  CAS  Google Scholar 

  • Maniotis AJ, Folberg R, Hess A, Seftor EA, Gardner LM, Pe’er J, Trent JM, Meltzer PS, Hendrix MJ (1999) Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol 155:739–752

    PubMed  CrossRef  CAS  Google Scholar 

  • Mazzieri R, Pucci F, Moi D, Zonari E, Ranghetti A, Berti A, Politi LS, Gentner B, Brown JL, Naldini L et al (2011) Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells. Cancer Cell 19:512–526

    PubMed  CrossRef  CAS  Google Scholar 

  • Milan SA, Yeo CJ (2012) Neuroendocrine tumors of the pancreas. Curr Opin Oncol 24:46–55

    PubMed  CrossRef  Google Scholar 

  • Mirza N, Fishman M, Fricke I, Dunn M, Neuger AM, Frost TJ, Lush RM, Antonia S, Gabrilovich DI (2006) All-trans-retinoic acid improves differentiation of myeloid cells and immune response in cancer patients. Cancer Res 66:9299–9307

    PubMed  CrossRef  CAS  Google Scholar 

  • Movahedi K, Guilliams M, Van den Bossche J, Van den Bergh R, Gysemans C, Beschin A, De Baetselier P, Van Ginderachter JA (2008) Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity. Blood 111:4233–4244

    PubMed  CrossRef  CAS  Google Scholar 

  • Murdoch C, Muthana M, Coffelt SB, Lewis CE (2008) The role of myeloid cells in the promotion of tumour angiogenesis. Nat Rev Cancer 8:618–631

    PubMed  CrossRef  CAS  Google Scholar 

  • O’Connor R, Clynes M, Dowling P, O’Donovan N, O’Driscoll L (2007) Drug resistance in cancer – searching for mechanisms, markers and therapeutic agents. Expert Opin Drug Metab Toxicol 3:805–817

    PubMed  CrossRef  Google Scholar 

  • Ostrand-Rosenberg S, Sinha P (2009) Myeloid-derived suppressor cells: linking inflammation and cancer. J Immunol 182:4499–4506

    PubMed  CrossRef  CAS  Google Scholar 

  • Paez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama H, Vinals F, Inoue M, Bergers G, Hanahan D, Casanovas O (2009) Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 15:220–231

    PubMed  CrossRef  CAS  Google Scholar 

  • Pan PY, Wang GX, Yin B, Ozao J, Ku T, Divino CM, Chen SH (2008) Reversion of immune tolerance in advanced malignancy: modulation of myeloid-derived suppressor cell development by blockade of stem-cell factor function. Blood 111:219–228

    PubMed  CrossRef  CAS  Google Scholar 

  • Pandit R, Lathers DM, Beal NM, Garrity T, Young MR (2000) CD34+ immune suppressive cells in the peripheral blood of patients with head and neck cancer. Ann Otol Rhinol Laryngol 109:749–754

    PubMed  CAS  Google Scholar 

  • Peters BA, Diaz LA, Polyak K, Meszler L, Romans K, Guinan EC, Antin JH, Myerson D, Hamilton SR, Vogelstein B et al (2005) Contribution of bone marrow-derived endothelial cells to human tumor vasculature. Nat Med 11:261–262

    PubMed  CrossRef  CAS  Google Scholar 

  • Potente M, Gerhardt H, Carmeliet P (2011) Basic and therapeutic aspects of angiogenesis. Cell 146:873–887

    PubMed  CrossRef  CAS  Google Scholar 

  • Priceman SJ, Sung JL, Shaposhnik Z, Burton JB, Torres-Collado AX, Moughon DL, Johnson M, Lusis AJ, Cohen DA, Iruela-Arispe ML et al (2010) Targeting distinct tumor-infiltrating myeloid cells by inhibiting CSF-1 receptor: combating tumor evasion of antiangiogenic therapy. Blood 115:1461–1471

    PubMed  CrossRef  CAS  Google Scholar 

  • Reddy GR, Kuo CC, Tan UK, Coumar MS, Chang CY, Chiang YK, Lai MJ, Yeh JY, Wu SY, Chang JY et al (2008) Synthesis and structure-activity relationships of 2-amino-1-aroylnaphthalene and 2-hydroxy-1-aroylnaphthalenes as potent antitubulin agents. J Med Chem 51: 8163–8167

    PubMed  CrossRef  CAS  Google Scholar 

  • Ricci-Vitiani L, Pallini R, Biffoni M, Todaro M, Invernici G, Cenci T, Maira G, Parati EA, Stassi G, Larocca LM et al (2010) Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells. Nature 468:824–828

    PubMed  CrossRef  CAS  Google Scholar 

  • Rolny C, Mazzone M, Tugues S, Laoui D, Johansson I, Coulon C, Squadrito ML, Segura I, Li X, Knevels E et al (2011) HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF. Cancer Cell 19:31–44

    PubMed  CrossRef  CAS  Google Scholar 

  • Schmid MC, Avraamides CJ, Dippold HC, Franco I, Foubert P, Ellies LG, Acevedo LM, Manglicmot JR, Song X, Wrasidlo W et al (2011) Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3kgamma, a single convergent point promoting tumor inflammation and progression. Cancer Cell 19:715–727

    PubMed  CrossRef  CAS  Google Scholar 

  • Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219:983–985

    PubMed  CrossRef  CAS  Google Scholar 

  • Sharma N, Seftor RE, Seftor EA, Gruman LM, Heidger PM Jr, Cohen MB, Lubaroff DM, Hendrix MJ (2002) Prostatic tumor cell plasticity involves cooperative interactions of distinct phenotypic subpopulations: role in vasculogenic mimicry. Prostate 50:189–201

    PubMed  CrossRef  Google Scholar 

  • Shirakawa K, Kobayashi H, Heike Y, Kawamoto S, Brechbiel MW, Kasumi F, Iwanaga T, Konishi F, Terada M, Wakasugi H (2002) Hemodynamics in vasculogenic mimicry and angiogenesis of inflammatory breast cancer xenograft. Cancer Res 62:560–566

    PubMed  CAS  Google Scholar 

  • Shojaei F, Wu X, Malik AK, Zhong C, Baldwin ME, Schanz S, Fuh G, Gerber HP, Ferrara N (2007a) Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nat Biotechnol 25:911–920

    PubMed  CrossRef  CAS  Google Scholar 

  • Shojaei F, Wu X, Zhong C, Yu L, Liang XH, Yao J, Blanchard D, Bais C, Peale FV, van Bruggen N et al (2007b) Bv8 regulates myeloid-cell-dependent tumour angiogenesis. Nature 450:825–831

    PubMed  CrossRef  CAS  Google Scholar 

  • Shojaei F, Singh M, Thompson JD, Ferrara N (2008) Role of Bv8 in neutrophil-dependent angiogenesis in a transgenic model of cancer progression. Proc Natl Acad Sci USA 105:2640–2645

    PubMed  CrossRef  CAS  Google Scholar 

  • Shojaei F, Wu X, Qu X, Kowanetz M, Yu L, Tan M, Meng YG, Ferrara N (2009) G-CSF-initiated myeloid cell mobilization and angiogenesis mediate tumor refractoriness to anti-VEGF therapy in mouse models. Proc Natl Acad Sci USA 106:6742–6747

    PubMed  CrossRef  CAS  Google Scholar 

  • Sica A, Larghi P, Mancino A, Rubino L, Porta C, Totaro MG, Rimoldi M, Biswas SK, Allavena P, Mantovani A (2008) Macrophage polarization in tumour progression. Semin Cancer Biol 18:349–355

    PubMed  CrossRef  CAS  Google Scholar 

  • Simon MP, Tournaire R, Pouyssegur J (2008) The angiopoietin-2 gene of endothelial cells is up-regulated in hypoxia by a HIF binding site located in its first intron and by the central factors GATA-2 and Ets-1. J Cell Physiol 217:809–818

    PubMed  CrossRef  CAS  Google Scholar 

  • Smith JK, Mamoon NM, Duhe RJ (2004) Emerging roles of targeted small molecule protein-tyrosine kinase inhibitors in cancer therapy. Oncol Res 14:175–225

    PubMed  Google Scholar 

  • Soda Y, Marumoto T, Friedmann-Morvinski D, Soda M, Liu F, Michiue H, Pastorino S, Yang M, Hoffman RM, Kesari S et al (2011) Transdifferentiation of glioblastoma cells into vascular endothelial cells. Proc Natl Acad Sci USA 108:4274–4280

    PubMed  CrossRef  CAS  Google Scholar 

  • Song S, Ewald AJ, Stallcup W, Werb Z, Bergers G (2005) PDGFRbeta+ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival. Nat Cell Biol 7:870–879

    PubMed  CrossRef  CAS  Google Scholar 

  • Srivastava MK, Bosch JJ, Thompson JA, Ksander BR, Edelman MJ, Ostrand-Rosenberg S (2008) Lung cancer patients’ CD4(+) T cells are activated in vitro by MHC II cell-based vaccines despite the presence of myeloid-derived suppressor cells. Cancer Immunol Immunother 57:1493–1504

    PubMed  CrossRef  CAS  Google Scholar 

  • Sun B, Zhang S, Zhao X, Zhang W, Hao X (2004) Vasculogenic mimicry is associated with poor survival in patients with mesothelial sarcomas and alveolar rhabdomyosarcomas. Int J Oncol 25:1609–1614

    PubMed  Google Scholar 

  • Takanami I, Takeuchi K, Kodaira S (1999) Tumor-associated macrophage infiltration in pulmonary adenocarcinoma: association with angiogenesis and poor prognosis. Oncology 57:138–142

    PubMed  CrossRef  CAS  Google Scholar 

  • Venneri MA, De Palma M, Ponzoni M, Pucci F, Scielzo C, Zonari E, Mazzieri R, Doglioni C, Naldini L (2007) Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer. Blood 109:5276–5285

    PubMed  CrossRef  CAS  Google Scholar 

  • Wang R, Chadalavada K, Wilshire J, Kowalik U, Hovinga KE, Geber A, Fligelman B, Leversha M, Brennan C, Tabar V (2010) Glioblastoma stem-like cells give rise to tumour endothelium. Nature 468:829–833

    PubMed  CrossRef  CAS  Google Scholar 

  • Welford AF, Biziato D, Coffelt SB, Nucera S, Fisher M, Pucci F, Di Serio C, Naldini L, De Palma M, Tozer GM et al (2011) TIE2-expressing macrophages limit the therapeutic efficacy of the vascular-disrupting agent combretastatin A4 phosphate in mice. J Clin Invest 121:1969–1973

    PubMed  CrossRef  CAS  Google Scholar 

  • Yang L, DeBusk LM, Fukuda K, Fingleton B, Green-Jarvis B, Shyr Y, Matrisian LM, Carbone DP, Lin PC (2004) Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell 6:409–421

    PubMed  CrossRef  CAS  Google Scholar 

  • Yang L, Huang J, Ren X, Gorska AE, Chytil A, Aakre M, Carbone DP, Matrisian LM, Richmond A, Lin PC et al (2008) Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis. Cancer Cell 13:23–35

    PubMed  CrossRef  CAS  Google Scholar 

  • Youn JI, Nagaraj S, Collazo M, Gabrilovich DI (2008) Subsets of myeloid-derived suppressor cells in tumor-bearing mice. J Immunol 181:5791–5802

    PubMed  CAS  Google Scholar 

  • Zeisberger SM, Odermatt B, Marty C, Zehnder-Fjallman AH, Ballmer-Hofer K, Schwendener RA (2006) Clodronate-liposome-mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach. Brit J Cancer 95:272–281

    PubMed  CrossRef  CAS  Google Scholar 

  • Zumsteg A, Christofori G (2009) Corrupt policemen: inflammatory cells promote tumor angiogenesis. Curr Opin Oncol 21:60–70

    PubMed  CrossRef  Google Scholar 

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Authors and Affiliations

  1. Departments of Neurological Surgery, University of California, Helen Diller Family Cancer Research Center, 1450 3rd Street, MC 0520, San Francisco, CA, 94158-9001, USA

    Lee Rivera, Melissa Pandika & Gabriele Bergers Ph.D.

  2. Brain Tumor Research Center, University of California, Helen Diller Family Cancer Research Center, San Francisco, CA, 94158, USA

    Lee Rivera, Melissa Pandika & Gabriele Bergers Ph.D.

  3. Anatomy, University of California, Helen Diller Family Cancer Research Center, San Francisco, CA, 94158, USA

    Gabriele Bergers Ph.D.

  4. UCSF Comprehensive Cancer Center, University of California, Helen Diller Family Cancer Research Center, 1450 3rd Street, MC 0520, San Francisco, CA, 94158-9001, USA

    Gabriele Bergers Ph.D.

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  1. Lee Rivera
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  2. Melissa Pandika
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  3. Gabriele Bergers Ph.D.
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Correspondence to Gabriele Bergers Ph.D. .

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Editors and Affiliations

  1. Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA

    Constantinos Koumenis

  2. Cancer Research, Gray Institute for Radiation Oncology, Oxford, United Kingdom

    Ester Hammond

  3. Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California, USA

    Amato Giaccia

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Rivera, L., Pandika, M., Bergers, G. (2014). Escape Mechanisms from Antiangiogenic Therapy: An Immune Cell’s Perspective. In: Koumenis, C., Hammond, E., Giaccia, A. (eds) Tumor Microenvironment and Cellular Stress. Advances in Experimental Medicine and Biology, vol 772. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5915-6_4

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