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Endothelial Progenitors in the Tumor Microenvironment

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Tumor Microenvironment

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1263))

Abstract

Tumor vascularization refers to the formation of new blood vessels within a tumor and is considered one of the hallmarks of cancer. Tumor vessels supply the tumor with oxygen and nutrients, required to sustain tumor growth and progression, and provide a gateway for tumor metastasis through the blood or lymphatic vasculature. Blood vessels display an angiocrine capacity of supporting the survival and proliferation of tumor cells through the production of growth factors and cytokines. Although tumor vasculature plays an essential role in sustaining tumor growth, it represents at the same time an essential way to deliver drugs and immune cells to the tumor. However, tumor vasculature exhibits many morphological and functional abnormalities, thus resulting in the formation of hypoxic areas within tumors, believed to represent a mechanism to maintain tumor cells in an invasive state.

Tumors are vascularized through a variety of modalities, mainly represented by angiogenesis, where VEGF and other members of the VEGF family play a key role. This has represented the basis for the development of anti-VEGF blocking agents and their use in cancer therapy: however, these agents failed to induce significant therapeutic effects.

Much less is known about the cellular origin of vessel network in tumors. Various cell types may contribute to tumor vasculature in different tumors or in the same tumor, such as mature endothelial cells, endothelial progenitor cells (EPCs), or the same tumor cells through a process of transdifferentiation. Early studies have suggested a role for bone marrow-derived EPCs; these cells do not are true EPCs but myeloid progenitors differentiating into monocytic cells, exerting a proangiogenic effect through a paracrine mechanism. More recent studies have shown the existence of tissue-resident endothelial vascular progenitors (EVPs) present at the level of vessel endothelium and their possible involvement as cells of origin of tumor vasculature.

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References

  1. Adighibe O, Leek RD, Fernandez-Mercado M, Hu J, Snell C, Gatter KC, Harris AL, Pezzella F (2016) Why some tumours trigger neovascularisation and others don’t: the story thus far. Chin J Cancer 35:18

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Alabi RO, Farber G, Blobel CP (2018) Intriguing roles for endothelial ADAM10/Notch signaling in the development of organ-specific vascular beds. Physiol Rev 98:2025–2061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Allen E, Jabouille A, Rivera LB, Lodewijckx I, Missiaen R, Steri V, Feyen K, Trawney J, Hanahan D, Michael IP, Bergers G (2017) Combined antiangiogenic and anti-PD-L1 therapy stimulates tumor immunity through HEV formation. Sci Transl Med 9:eaak9679

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Alphonse RS, Vadivel A, Fung M, Shelley WC, Critser PJ, Ionescu L, O’Reilly M, Ohls RK, McConaghy S, Eaton F, Zhong S, Yoder M, Thébaud B (2014) Existence, functional impairment, and lung repair potential of endothelial colony-forming cells in oxygen-induced arrested alveolar growth. Circulation 129:2144–2157

    Article  PubMed  PubMed Central  Google Scholar 

  5. Alphonse RS, Vadivel A, Zhong S, McConaghy S, Ohis R, Yoder MC, Thébaud B (2015) The isolation and culture of endothelial colony-forming cells from human and rat lungs. Nat Protoc 10:16971708

    Article  CAS  Google Scholar 

  6. Alvarez DF, Huang I, King JA, El Zarrad MK, Yoder MC, Stevens T (2008) Lung microvascular endothelium is enriched with progenitor cells that exhibit vasculogenic capacity. Am J Physiol Lung Cell Mol Physiol 294:L419–L430

    Article  CAS  PubMed  Google Scholar 

  7. Ameratunga M, Pavlakis N, Wheeler N, Grant R, Simes J, Karasaw M (2018) Anti-angiogenic therapy for high-grade glioma. Cochrane Database Syst Rev 11:CD008218

    PubMed  Google Scholar 

  8. Amoozgar Z, Jain RK, Duda DG (2019) Role of apelin in glioblastoma vascularization and invasion after anti-VEGF therapy: what is the impact on the immune system? Cancer Res 79:2104–2106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Apte RS, Chen DS, Ferrara N (2019) VEGF in signaling and disease: beyond discovery and development. Cell 176:1248–1264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Asahara T, Murdrara T, Sullivan A, Silbver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner GM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967

    Article  CAS  PubMed  Google Scholar 

  11. Aung PP, Parra ER, Barua S, Sui D, Ning J, Mino B, Ledesma DA, Curry JL, Nagarajan P, Torras-Cabala CA, Efstathion E, Hoang AG, Wong MK, Wargo JA, Lazar AJ, Rao A, Prieto VG, Wistuba I, Tetzlaff MT (2019) B7-H3 expression in Merkel cell carcinoma-associated endothelial cells correlates with locally aggressive primary tumor features and increased vascular density. Clin Cancer Res 25:3455–3467

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Bachawal SV, Jensen KC, Wilson KE, Tian L, Lutz AM, Willmann JK (2015) Breast cancer detection by B7-H3-targeted ultrasound molecular imaging. Cancer res 75: 2501-2509

    Google Scholar 

  13. Bao S, Wu Q, Sathorsnusumetee S, Hao Y, Li Z, Hjelmeland AB, Shi Q, McLendon RE, Bigner DD, Rich JN (2006) Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Res 66:7843–7848

    Article  CAS  PubMed  Google Scholar 

  14. Bao R, Wang Y, Lai J, Zhu H, Zhao Y, Li S, Li N, Huang J, Yang Z, Wang F, Liu Z (2019) Enhancing anti-PD-1/PD-L1 immune checkpoint inhibitory cancer therapy by CD276-targeted photodynamic ablation of tumor cells and tumor vasculature. Mol Pharmacol 16:339–348

    Article  CAS  Google Scholar 

  15. Beekman R, Amador V, Campo E (2018) SOX11, a key oncogenic factor in mantle cell lymphoma. Curr Opin Hematol 25:299–306

    Article  CAS  PubMed  Google Scholar 

  16. Berta J, Kenessey I, Dobos J, Tovari J, Klepetko W, Jan Ankersmit H, Hegedus B, Renyi-Vamos F, Varga J, Lorincz Z, Paku S, Ostoros G, Rozsas A, Timar J, Dome B (2010) Apelin expression in human non-small cell lung cancer: role in angiogenesis and prognosis. J Trorac Oncol 5:1120–1129

    Article  Google Scholar 

  17. Blaser BW, Zon LI (2018) Making HSCs in vitro: don’t forget the hemogenic endothelium. Blood 132:1372–1378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Blatchley MR, Hall F, Wang S, Pruitt HC, Gerecht S (2019) Hypoxia and matrix viscoelasticity sequentially regulate endothelial progenitor cluster-based vasculogenesis. Sci Adv 5:eaau7518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Brem S, Cotran R, Folkman J (1972) Tumor angiogenesis: a quantitative method of histologic grading. J Natl Cancer Inst 48:347–356

    CAS  PubMed  Google Scholar 

  20. Bridgeman VL, Vermeulen PB, Foo S, Bilecz A, Daley F, Kostaras E, Nathan MR, Wan E, Frentzas S, Schweiger T, Hegedus B, Hoetzenecker K, Renyi-Vamos F, Kuczynski EA (2017) Vessel co-option is common in human lung metastases and mediates resistance to anti-angiogenic therapy in preclinical lung metastasis model. J Pathol 241:362–374

    Article  CAS  PubMed  Google Scholar 

  21. Caivano A, La Rocca F, Laurenzana I, Annese T, Tamma R, Famigliari U, Simeon V, Trino S, De Luca L, Villani O, Berardi S, Basile A, Vacca A, Saglio G, Del Vecchio L, Musto P, Cilloni D (2017) Epha3 acts as proangiogenic factor in multiple myeloma. Oncotarget 8:34298–34309

    Article  PubMed  PubMed Central  Google Scholar 

  22. Cao Z, Scandura JM, Inghirami GG, Shido K, Ding BS, Rafii S (2017) Molecular checkpoint decisions made by subverted vascular niche transform indolent tumor cells into chemoresistant cancer stem cells. Cancer Cell 31:110–126

    Article  CAS  PubMed  Google Scholar 

  23. Cardesa-Salzmann TM, Colomo L, Gutierrez G, Chan WC, Weisenburger D, Climent F, Gonzalez-Barca E, Mercadal S, Arenillas L, Serrano S, Tubbs R, Delabie J, Gascoyne RD, Connors JM, Mate JL, Rimsza L, Braziel R, Rosenwald A, Lenz G, Wright G, Jaffe ES, Staudt L, Jares P, Lopez-Guillermo A, Campo E (2011) High microvessel density determines a poor outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus chemotherapy. Haematologica 96:996–1001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Carlson P, Dasgupta A, Grzelak CA, Kim J, Barrett A, Coleman IM, Shor RE, Goddard ET, Dai J, Schweitzer EM, Lim AR, Crist SB, Cherech DA, Nelson PS, Hansen KC, Ghajar CM (2019) Targeting the perivascular niche sensitizes disseminated tumour cells to chemotherapy. Nat Cell Biol 21:238–250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Carmeliet P (2005) Angiogenesis in life, disease and medicine. Nature 438:932–936

    Article  CAS  PubMed  Google Scholar 

  26. Carmeliet P, Jain RK (2011) Molecular mechanisms and clinical applications of angiogenesis. Nature 473:298–306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Centelmo AR, Conradi LC, Brajic A, Goveia J, Kalucka J, Picher A, Chaturvedi P, Hol J, Thienpont B, Teuwen LA, Schoors S, Boeckx B, Vriens J, Kuchnio A, Veys K, Cruys B, Finotto L, Trepsa L (2016) Inhibition of the glycolytic activator PFKFB3 in endothelium induces tumor vessel normalization, impairs metastasis, and improves chemotherapy. Cancer Cell 30:968–985

    Article  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Chauhan D, Ray A, Viktorsson K, Spira J, Paba-Prada C, Munshi N, Richardson P, Lowensohn R, Anderson KC (2013) In vitro and in vivo antitumor activity of a novel alkylating agent, melphalan-flufenamnide, against multiple myeloma cells. Clin Cancer Res 19:3019–3031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Chen H, Gordon MS, Campbell RA, Li M, Wang CS, Lee HJ, Sanchez E, Manvak SJ, Gui D, Shalitin D, Said J, Chang Y, Deuel TF, Baritaki S, Bonavida B, Berenson JR (2007) Pleiotroiphin is highly expressed by myeloma cells and promotes myeloma tumor growth. Blood 110:287–295

    Article  CAS  PubMed  Google Scholar 

  31. Chen H, Campbell RA, Chang Y, Li M, Wang CS, Li J, Sanchez E, Share M, Steinberg J, Berenson A, Shalitin D, Zeng Z, Gui D, Perez-Pinera P, Berenson RJ, Said J, Bonavida B, Deuel TF, Berenson JR (2009) Pleiotrophin produced by multiple myeloma induces transdifferentiation of monocytes into vascular endothelial cells: a novel mechanism of tumor-induced vasculogenesis. Blood 113:1992–2002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chen P, Huang Y, Bong R, Ding Y, Song N, Wang X, Song X, Luo Y (2011) Tumor-associated macrophages promote angiogenesis and melanoma growth via adrenomedullin in a paracrine and autocrine manner. Clin Cancer Res 17:7230–7239

    Article  CAS  PubMed  Google Scholar 

  33. Chen W, Xia P, Wang H, Tu J, Liang X, Zhang X, Li L (2019) The endothelial tip-stalk cell selection and shuffling during angiogenesis. J Cell Commun Signal in Press 13(3):291–301

    Article  Google Scholar 

  34. Cheng L, Huang Z, Zhou W, Wu Q, Donnola S, Liu JK, Fang X, Sloan AE, Mao Y, Lathia JD, Min W, McLendon RE, Rich JN, Bao S (2013) Glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth. Cell 153:139–152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Cloughesy TF, Mochizuki AY, Orpilla JR, Hugo W, Lee AH, Davidson TB, Wang AC, Ellingson BM, Ritlewski JA, Sanders CM, Kawaguchi ES, Du L, Li G, Yong WHJ, Gaffey SC, Cohen AL, Mellinghoff IK, Lee EQ, Reardon DA, O’Brien BJ, Butowski NA, Nghiemphu PL, Clarke JL, Arrillaga-Romany IC, Colmasn H, Kaleyt TJ, de Groiot JF, Liau LM, Wen PY, Prins RM (2019) Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma. Nat Med 25:477–486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Crispen PL, Sheinin Y, Roth TJ, Lohse CM, Kuntz SM, Frigola X, Thopson RH, Boorjian SA, Dong H, Leibovich BC, Blute ML, Kwon ED (2008) Tumor cell and tumor vasculature expression of B7-H3 predict survival in clear cell renal cell carcinoma. Clin Cancer Res 14:5150–5157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Cui C, Chen X, Liu Y, Cao B, Xing Y, Liu C, Yang F, Li Y, Yang T, Hua L, Tian M, Wei Y, Gong Y, Jiang J (2018) β1,4-Galactosyltransferase V activates Notch 1 signaling in glioma stem-like cells and promotes their transdifferentiation into endothelial cells. J Biol Chem 293:2219–2230

    Article  CAS  PubMed  Google Scholar 

  38. De la Puente P, Muz B, Azab F, Azab AK (2013) Cell trafficking of endothelial progenitor cells in tumor progression. Clin Cancer Res 19:3360–3368

    Article  PubMed  CAS  Google Scholar 

  39. De Palma M, Biziato D, Petrova TV (2017) Microenvironmental regulation of tumor angiogenesis. Nat Rev Cancer 17:457–474

    Article  PubMed  CAS  Google Scholar 

  40. De Pascalis I, Morgante L, Pacioni S, D’Alessandris QG, Giannetti S, Martini M, Ricci-Vitiani L, Malinverno M, Dejana E, Larocca LM, Pallini R (2018) Endothelial trans-differentiation in glioblastoma recurring after radiotherapy. Mod Pathol 31:1361–1366

    Article  PubMed  CAS  Google Scholar 

  41. Dimitrova N, Gocheva V, Bhutkar A, Resnick R, Jong RM, Miller KM, Bendor J, Jacks T (2016) Stromal expression of miR-143/145 promotes neoangiogenesis in lung cancer development. Cancer Discov 6:188–201

    Article  CAS  PubMed  Google Scholar 

  42. Donnem T, Reynolds AR, Kuczynski EA, Gatter K, Vermeulen PB, Kerbel RS, Harris AL, Pezzella F (2018) Non-angiogenic tumours and their influence on cancer biology. Nat Rev Cancer 18:323–336

    Article  CAS  PubMed  Google Scholar 

  43. Donovan P, Patel J, Dight J, Wong HY, Sim SL, Murigneux V, Francois M, Khosrotehrani K (2019) Endovascular progenitors infiltrate melanomas and differentiate towards a variety of vascular beds promoting tumor metastasis. Nat Commun 10:18

    Google Scholar 

  44. Du R, Lu KV, Petritsch C, Liu P, Ganss R, Passegué E, Song H, Vandenberg S, Johnson RS, Werb Z, Bergers G (2002) HIF1alpha induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell 13:206–220

    Article  CAS  Google Scholar 

  45. Du H, Hirabayashi K, Ahn S, Kren NP, Montgomery SA, Wang X, Tiruthani K, Mirlekar B, Michaud D, Greene K, Herrera SG, Xu Y, Sun C, Chen Y, Ma X, Ferrone CR, Pylayeva-Gupta Y, Yeh JJ, Liu R, Savoldo B, Ferrone S, Dotti G (2019) Antitumor responses in the absence of toxicity in solid tumors by targeting B7-H3 via chimeric antigen receptor T cells. Cancer Cell 35:221–237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Duong T, Proulx ST, Luciani P, Leroux JC, Detmar M, Koopman P, Francois M (2012) Genetic ablation of SOX18 function suppresses tumor lymphangiogenesis and metastasis of melanoma in mice. Cancer Res 72:3105–3114

    Article  CAS  PubMed  Google Scholar 

  47. Duong T, Koltowska K, Pichol-Thievend C, Le Guen L, Fontaine F, Smith KA, Truong V, Skoczylas R, Stacker SA, Achen MG, Koopman P, Hogan BM, Francois M (2014) VEGFD regulates blood vascular development by modulating SOX18 activity. Blood 123:1102–1112

    Article  CAS  PubMed  Google Scholar 

  48. Eldridge L, Moldobaeva A, Zhong Q, Jenkins J, Snyder M, Brown RH, Mitzner W, Wagner EM (2016) Bronchial artery angiogenesis drives lung tumor growth. Cancer Res 76:5962–5969

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Facon T, Kumar S, Plesner T, Orlowski RZ, Moreau P, Bahlis N, Basu S, Nahi H, Hulin C, Quach H, Goldschmidt H, O’Dwyver M, Perrot A, Venner CP, Weisel K, Mace JR, Raje N, Attal M, Tiab M, Macro M, Frenzel L, Leleu X, Ahmadi T, Chiu C, Wang J, Van Rampelbergh R, Uhlar CM, Kobos R, Qi M, Usmani SZ, MAIA trial investigators (2019) Duratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med 380:2104–2115

    Article  CAS  PubMed  Google Scholar 

  50. Farha S, Asossingh K, Xu W, Sharp J, George D, Comhair S, Park M, Tang WH, Loyd JE, Theil K, Tubbs R, His E, Lichtin A, Ezurum SC (2011) Hypoxia-inducible factors in human pulmonary arterial hypertension: a link to the intrinsic myeloid abnormalities. Blood 117:3485–3493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Folkins C, Shaked Y, Man S, Tang T, Lee CR, Zhu Z, Hoffman RM, Kerbel RS (2009) Glioma stem-like cells promote tumor angiogenesis and vasculogenesis via vascular endothelial growth factor and stromal-derived factor 1. Cancer Res 69:7243–7251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Fontaine F, Overman J, Moustaqil M, Mamidyala S, Salim A, Narasimhan K, Prokoph N, Robertson AAB, Lua L, Alexandrov K, Koopman P, Capon RJ, Sierecki E, Jauch R, Cooper MA, Zuegg J, Francois M (2017) Small-molecule inhibitors of the SOX18 transcription factor. Cell Chem Biol 24:346–359

    Article  CAS  PubMed  Google Scholar 

  53. Francois M, Caprini A, Hosking B, Orsenigo F, Wilhelm D, Browne C, Paavonen K, Karnezis T, Shavan R, Downer M, Davidson T, Tutt DF, Cheah KS, Stacker SA, Muscat GE, Achen MG, Dejana E, Koopmenm P (2008) SOX18 induces development of the lymphatic vasculature in mice. Nature 456:643–647

    Article  CAS  PubMed  Google Scholar 

  54. Frantzas S, Simoneau E, Bridgeman VL, Vermeulen PB, Foo S, Kostaras E, Natahan M, Wothrspoon A, Gao ZH, Shi Y, Van den Eynden G, Daley F, Peckitt C, Tan X, Salman A, Lazaris A (2016) Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases. Nat Med 22:1294–1302

    Article  CAS  Google Scholar 

  55. Ganguly D, Cai C, Sims MM, Yang CH, Thomas M, Cheng J, Saad AG, Pfeffer LM (2019) APELA expression in glioma, and its association with patient survival and tumor grade. Pharmaceuticals 12:E45

    Article  PubMed  CAS  Google Scholar 

  56. Ge H, Luo H (2018) Overview of advances in vasculogenic mimicry-a potential target for tumor therapy. Cancer Managem Res 10:2429–2437

    Article  CAS  Google Scholar 

  57. Georgouli M, Herraiz C, Crosas-Molist E, Fanshawe B, Maiques O, Perdrix A, Pandya P, Rodriguez-Hernandez I, Ilieva KM, Cantelli G, Karagiannis P, Mele S, Lam H, Josephs DH, Matias-Guiu X, Marti RM, Nestle FO, Orgaz JL, Malanchi I, Fruhwirth GO, Karagiannis SN, Sanz-Moreno V (2019) Regional activation of myosin II in cancer cells drives tumor progression via a secretory cross-talk with the immune microenvironment. Cell 176:757–774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Golebiewska A, Bougnaud S, Stieber D, Brons N, Vallar L, Hertel F, Klink B, Schrock E, Bjerkvig R, Nichou SP (2013) Side population in human glioblastoma is non-tumorigenic and characterizes brain endothelial cells. Brain 136:1462–1475

    Article  PubMed  PubMed Central  Google Scholar 

  59. Griveau A, Seano G, Shelton SJ, Kupp R, Johangiri A, Obernier K, Krishnan S, Lindberg OR, Yuen TJ, Tien AC, Sabo JK, Wang N, Chen I, Kloepper J, Larrouquere L, Ghosh M, Tirosh I, Huillard E, Alvarez-Buylla A, Oldham MC, Persson AI, Weiss WA, Batchelor TT, Stemmer-Rachamimov A, Suvà ML, Phillips JJ, Aghi MK, Mehta S, Jain RK, Rowitch DH (2018) A glial signature and Wnt/7 signaling regulate glioma-vascular interactions and tumor microenvironment. Cancer Cell 33:874–889

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Guadall A, Lesteven E, Letort G, Awan Toor S, Delord M, Pognant D, Brusson M, Verger E, Masiah N, Giraudier S, Larghero J, Vanneaux V, Chonmienne C, El Nemer W, Cassinat B, Kiladjian JJ (2018) Endothelial cells harbouring the JAK2V617F mutation display pro-adherent pro-thrombotic features. Thromb Hemost 118:1586–1599

    Article  Google Scholar 

  61. Guy A, Gourdou-Latsyszenok V, Le Lay N, Peghaire C, Kilani B, Dias JV, Duplaa C, Renault MA, Denis C, Villel JL, Boulaftali Y, Jandrot-Perrus M, Couffinhal T, James C (2019) Vascular endothelial cell expression of JAK2V617F is sufficient to promote a pro-thrombotic state due to increased P-selectin expression. Haematologica 104:70–81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Hagdahl E, Bachmann IM, Schuster C, Ladstein RG, Akslen LA (2019) Prognostic value of uPAR expression and angiogenesis in primary and metastatic melanoma. PLoS One 14:e0210399

    Article  CAS  Google Scholar 

  63. Hardee ME, Zagzagh D (2012) Mechanisms of glioma-associated neovascularization. Am J Pathol 181:1126–1141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Harford-Wright E, Andre-Gregoire G, Jacobs KA, Treps L, Le Gouidec S, Leclair HM, Gonzalez-Djest S, Roux Q, Guillonneau F, Lossouam D, Olivere L, Vallette FM, Foufelle F, Vallet P, Davenport AP, Glen RC, Bidere N, Gavard J (2017) Pharmacological targeting of apelin impairs glioblastoma growth. Brain 140:2939–2954

    Article  PubMed  PubMed Central  Google Scholar 

  65. Helker CS, Schuemann A, Pollmann C, Chng SC, Kiefer F, Reversade B, Herzog W (2015) The hormonal peptide Elabela guides angioblast to the midline during vasculogenesis. Elife 4. https://doi.org/10.7554/seLife.06726.001

  66. Hermansen SE, Lund T, Kaòlstad T, Ytrehus K, Myrmel T (2011) Adrenomeullin augments the angiogenic potential of late outgrowth endothelial progenitor cells. Am J Cell Physiol 300:C783–C791

    Article  CAS  Google Scholar 

  67. Hida K, Maishi N, Akiyama K, Ohmura-Kakutani H, Torii C, Ohga N, Osawa T, Kikuchi H, Morimoto H, Shindoh M, Shinohara N, Hida Y (2017) Tumor endothelial cells with high aldehyde dehydrogenase activity show drug resistance. Cancer Sci 108:2195–2203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Hillen F, van de Winkel A, Creytens D, Vermeulen AH, Griffioen AW (2006) Proliferating endothelial cells, but not microvessel density, are a prognostic parameter in human cutaneous melanoma. Melanoma Res 16:453–457

    Article  PubMed  Google Scholar 

  69. Hindson J (2019) Targeting endovascular progenitors control cancer. Nat Rev Cancer 19:1298–1130

    Google Scholar 

  70. Hogan B, Barkauskas CE, Chapman HA, Epstein JA, Jain R, Hsia C, Niklason L, Calle E, Le A, Randell SH, Rock J, Snitow M, Krummel M, Stripp BR, Vu T, White ES, Whitsett JA, Morrisey EE (2014) Repair and regeneration of the respiratory system: complexity, plasticity, and mechanisms of lung stem cells function. Cell Stem Cell 15:123–138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Hu J, Bianchi F, Ferguson M, Cesario A, Margaritora S, Granone P, Goldstraw P, Tetlow M, Ratcliffe C, Nicholson AG, Harris A, Gatter K, Pezzella F (2005) Gene expression signature for angiogenic and nonangiogenic non-small-cell lung cancer. Oncogene 24:1212–1219

    Article  CAS  PubMed  Google Scholar 

  72. Hu B, Wang YA, Hua S, Sauvé CEG, Ong D, Lan ZD, Chang Q, Ho YW, Monasterio M, Lu X, Zhong Y, Zhang J, Deng P, Tan Z, Wang G, Liao WT, Cortey LJ, Yan H, Zhang J, You Y, Liu N, Cal L, Finocchiaro G, Phillipos JJ, Berger MS, Spring DJ, Hu J, Sulma EP, Fuller GN, Chin L, Verhaak R, DePinho RA (2016) Epigenetic activation of WNT5A drives glioblastoma stem cell differentiation and invasive growth. Cell 167:1281–1295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Ingram DA, Mead LE, Tanaka H, Meade V, Fenoglio A, Mortell K (2004) Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood 104:2752–2760

    Article  CAS  PubMed  Google Scholar 

  74. Ishige-Wada M, Kwon SM, Eguchi M, Hozumi K, Iwaguro H, Matsumoto T, Fukuda N, Mugishima H, Masuda AT (2016) Jagged-1 signaling in the bone marrow microenvironment promotes endothelial progenitor cell expansion and commitment of CD133+ human cord blood cells for postnatal vasculogenesis. PLoS One 11:e0166660

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Jain RK (2001) Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 7:987–989

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  77. Jeon HM, Kim SH, Jin X, Park JB, Kim SH, Joshi K, Nakano I, Kim H (2014) Crosstalk between glioma-initiating cells and endothelial cells drives tumor progression. Cancer Res 74:4482–4492

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Johansson-Percival A, He B, Li ZJ, Kjellen A, Russell K, Li J, Larma I, Ganas R (2017) De novo induction of intratumoral lymphoid structures and vessel normalization enhances immunotherapy in resistant tumors. Nat Immunol 18:1207–1217

    Article  CAS  PubMed  Google Scholar 

  79. Kakolyris S, Gatromanoiaki A, Koukourakis M, Leigh IM, Georgoulias V, Kanavarios P, Sivridis E, Gatter KC, Harns AL (1999) Assessment of vascular maturation in non-small cell lung cancer using a novel basement membrane component, LH39: correlation with p53 and angiogenic factor expression. Cancer Res 59:5602–5607

    CAS  PubMed  Google Scholar 

  80. Kashani-Sabet M, Sagebiel RW, Ferreira CM, Nosrati M, Miller JR 3d (2002) Tumor vascularity in the prognostic assessment of primary cutaneous melanoma. J Clin Oncol 20:1826–1183

    Article  PubMed  Google Scholar 

  81. Katayama Y, Uchino J, Chihara Y, Tamiya N, Kaneko Y, Yamada T, Takayama K (2019) Tumor neovascularization and developments in therapeutics. Cancers 11:316

    Article  CAS  PubMed Central  Google Scholar 

  82. Kawasaki T, Nishiwaki T, Sekine A, Nishimura R, Suda R, Urushibara T, Suzuki T, Takayanagi S, Terada J, Sakao S, Tatsumi K (2015) Vascular repair by tissue resident endothelial progenitor cells in endotoxin-induced lung injury. Am J Respir Cell Mol Biol 53:500–512

    Article  CAS  PubMed  Google Scholar 

  83. Kidoya H, Kunii N, Naito H, Marumatsu F, Okamoto Y, Nakayama T (2012) The apelin/APJ system induces maturation of the tumor vasculature and improves the efficiency of immune therapy. Oncogene 31:3254–3264

    Article  CAS  PubMed  Google Scholar 

  84. Kim I, Koh Y (2017) Taking aim at Sox18. Elife 6:e24238

    Article  PubMed  PubMed Central  Google Scholar 

  85. Kim H, Huang L, Critser PJ, Yang Z, Chan RJ, Wang L, Carlesso N, Voytik-Harbin SL, Bernstein ID, Yoder MC (2015) Notch ligand delta-like 1 promotes in vivo vasculogenesis in human cord blood-derived endothelial colony forming cells. Cytotherapy 17:579–592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Kim IK, Kim K, Lee E, Oh DS, Park CS, Park S, Yang JM, Kim JH, Kim HS, Shima DT, Kim JH, Hong SH, Cho YH, Kim YH, Park JB, Koh GY, Ju YS, Lee HK, Lee S, Kim I (2018) Sox7 promotes high-grade glioma by increasing VEGFR2-mediated vascular abnormality. J Exp Med 215:963–983

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Kioi M, Vogel H, Schultz G, Hoffman RM, Harsh GR, Brown JM (2010) Inhibition of vasculogenesis, but not angiogenesis, prevents the recurrence of glioblastoma after irradiation in mice. J Clin Invest 120:694–705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Kuczynski EA, Vermeulen PB, Pezzella F, Kerbel RS, Reynolds AR (2019) Vessel co-option in cancer. Nat Rev Clin Oncol in Press 16:469–493

    Article  CAS  Google Scholar 

  89. Kumar S, Witzig TE, Timm M, Haug J, Wellik L, Kimlinger TK, Greipp PR, Rajikumar SV (2004) Bone marrow angiogenic ability and expression of angiogenic cytokines in myeloma: evidence favoring loss of marrow angiogenesis inhibitory activity with disease progression. Blood 104:1159–1165

    Article  CAS  PubMed  Google Scholar 

  90. Kumar S, Sharife H, Kreisel T, Mogilevsky M, Bar-Lev L, Grunewald M, Aizenshtein E, Karni R, Paldor I, Shlomi T, Keshet E (2019) Intra-tumoral metabolic zonation and resultant phenotypic diversification are dictated by blood vessel proximity. Cell Metab 30:1–11

    Article  CAS  Google Scholar 

  91. Laubach JP, Liu CJ, Raje NS, Yee AJ, Armand P, Schlossman RL, Rosenblatt J, Hedlund J, Martin M, Reynolds C, Shain KH, Zackon I, Stampleman L, Henrick P, Rivotto B, Hornburg KTV, Dumke HJ, Chuma S, Savell A, Handisides DR, Kroll S, Anderson KC, Richardson PG, Ghobrial IM (2019) A phase I/II study of evofosfamide, a hypoxia-activated prodrug with or without bortezomib in subjects with relapsed/refractory multiple myeloma. Clin Cancer Res 25:478–486

    Article  PubMed  CAS  Google Scholar 

  92. Lee JH, Lee JE, Kahng JY, Kim SH, Park JS, Yoon SJ, Um JY, Kim WK, Lee JK, Park J, Kim EH, Lee JH, Ching WS, Ju YS, Park SH, Chang JH, Kang SG, Lee JH (2018) Human glioblastoma arises from subventricular zone cells with low-level driver mutations. Nature 560:243–247

    Article  CAS  PubMed  Google Scholar 

  93. Lewis DM, Park KM, Tang V, Yu Y, Pak K, Eisnger-Mathason TS, Simon MC, Gerecht S (2016) Intratumoral oxygen gradients mediate sarcoma cell invasion. Proc Natl Acad Sci USA 113:9292–9297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Lewis DM, Pruitt H, Jain N, Ciccaglione M, McCaffery JM, Xia Z, Weber K, Eisinger-Mathason TSK, Gerecht S (2019) A feedback loop between hypoxia and matrix stress relaxation increases oxygen-axis migration and metastasis. Cancer Res 79:1981–1995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Li Z, Bao S, Wu Q, Wang H, Eyler C, Sathornsumetee S, Shi Q, Cao Y, Lathia J, McLendon RE, Hjelmeland AB, Rich JN (2009) Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell 15:501–513

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Li L, Li JCV, Yang H, Zhang X, Liu LL, Li Y, Zeng TT, Zhu YH, Li XD, Li Y, Xie D, Fu L, Fuan XY (2019) Expansion of cancer stem cell pool initiates lung cancer recurrence before angiogenesis. Proc Natl Acad Sci USA 115:E8948–E8957

    Google Scholar 

  97. Lin CH, Kaushansky K, Zhan H (2016) JAK2V617F-mutant vascular niche contributes to JAK2V617F clonal expansion in myeloproliferative neoplasms. Blood Cells Mol Dis 62:42–48

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Lin CH, Zhang Y, Kaushansky K, Zhan H (2018) JAK2V617F-bearing vascular niche enhances malignant hematopoietic regeneration following radiation injury. Haematologica 103:1160–1168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Liu XM, Zhang QP, Mu YG, Zhang XH, Sai K, Pang JC, Ng HK, Chen ZP (2011) Clinical significance of vasculogenic mimicry in human gliomas. J Neuro-Oncol 105:173–179

    Article  CAS  Google Scholar 

  100. Liu Q, Huang X, Zhang H, Tian X, He L, Yang R, Yan Y, Wang QD, Gillich A, Zhou B (2015) c-kit+ cells adopt vascular endothelial but not epithelial cell fates during lung maintenance and repair. Nat Med 21:866–868

    Article  CAS  PubMed  Google Scholar 

  101. Liu M, Zhang L, Marsboom G, Jambusaria A, Xiong S, Toth PT, Benevolenskaya EV, Rehman J, Malik AB (2019a) Sox17 is required for endothelial regeneration following inflammation-induced vascular injury. Nat Commun 10:2126

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Liu XM, LI F, Yang YT, Xu XD, Chen JS, Chen TL, Chen HJ, Zhu YB, Lin JY, Li Y, Xie XM, Sun XL, Ke YQ (2019b) IGFB2 promotes vasculogenic mimicry formation via regulating CD144 and MMP2 expression in glioma. Oncogene 38:1815–1831

    Article  CAS  PubMed  Google Scholar 

  103. Lombardi G, De Salvo GL, Brandes AA, Eoli M, Rudà R, Faedi M, Lolli I, Pace A, Daniele B, Pasqualetti F, Rizzato S, Bellu L, Pambuku A, Farina M, Magui G, Indraccolo S, Gardiman MP, Soffietti R, Zanogel V (2019) Regorafenib compared with lomustine in patients with relapsed glioblastoma (REGOMA): a multicentre, open-label, randomised, controlled, phase 2 trial. Lancet Oncol 20:110–119

    Article  CAS  PubMed  Google Scholar 

  104. Lukowski SW, Patel J, Andersen SB, Sim SL, Wong HY, Tay J, Winkler I, Powell JE, Khosrotehrani K (2019) Single-cell transcriptional profiling of aortic endothelium identifies a hierarchy from endovascular progenitors to differentiated cells. Cell Rep 27:2748–2758

    Article  CAS  PubMed  Google Scholar 

  105. McClelland MR, Carkskadon SL, Zhao L, White ES, Beer DG, Orringer MB, Pickens A, Chang AC, Arenberg DA (2007) Diversity of the angiogenic phenotype in non-small cell lung cancer. Am J Respir Cell Mol Biol 36:343–350

    Google Scholar 

  106. Majzner RG, Theruvath JL, Nellan A, Heitzeneder S, Cui Y, Mount CW, Rietberg SP, Linde MH, Xu P, Rota C, Sotillo E, Labanieh L, Lee DW, Orentas RJ, Dimitrov DS, Zhu Z, Croix BS, Delaidelli A, Sekunova A, Bonvini E, Mitra SS, Quezado MM, Majeti R, Monje M, Sorensen PHB, Maris JM, Mackall CL (2019) CAR T cell targeting B7-H3, a pan-cancer antigen, demonstrate potent preclinical activity against pediatric solid tumors and brain tumors. Clin Cancer Res 25:2560–2574

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  107. Marcu R, Choi YJ, Xue J, Fortin CL, Wang Y, Nagao RJ, Xu J, MacDonald JW, Bammler TK, Murry CE, Muczynski K, Stevens KR, Himmelfarb J, Schwartz SM, Zheng Y (2018) Human organ-specific endothelial cell heterogeneity. iScience 4:20–235

    Google Scholar 

  108. Martin JD, Seano G, Jain RK (2019) Normalizing function of tumor vessels: progress, opportunities, and challenges. Annu Rev Physiol 81:505–531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Mastrella G, Hou M, Li M, Stoecklein VM, Volmain NNM, Mileteic H, Reinhard S, Herold-Mende CC, Kleber S, Eisoenhut K, Gargiulo G, Symowitz M, Vescovi AL, Horelr PN, Pennonga JM, Wagner E, Mittebron M, Bjervig R, Hambadzumyan D, Schuller U, Tonn JC, Modke J, Glon R, Kalin RE (2019) Targeting APLN/APLNR improves anti-angiogenic efficiency and blunts proinvasive side effects of VEGFA/VEGFR2-blockade in glioblastoma. Cancer Res 79:2298–2313

    Article  CAS  PubMed  Google Scholar 

  110. McDermott DF, Huseni MA, Atkins MB, Motzer RJ, Rini BI, Escudier B, Fong L, Joseph RW, Pal SK, Reeves JA, Sznol M, Hainswoth J, Rathmell WK, Stadler WM, Hutsion T, Gore ME, Ravaud A, Bracarda S, Suarez C, Danielli R, Gruenwald V, Chouiri TK, Nickles D, Jhunjhunwala S, Piault-Louis E, Thobhani A, Qiu J, Chen DS, Hedge PS, Schiff C, Fine GD, Powles T (2018) Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. Nat Med 24:749–757

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. McDonald AI, Shirali AS, Aragon R, Ma F, Hernandez G, Vaughn DA, Mack JJ, Lim TY, Sunshine H, Zhao P, Kalinichenko V, Hai T, Pellegrini M, Ardehali R, Iruela-Arispe ML (2018) Endothelial regeneration of large vessels is a biphasic process driven by local cells with distinct proliferative capacities. Cell Stem Cell 23:210–225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Mead AJ, Mullally A (2017) Myeloproliferative neoplasm stem cells. Blood 129:1607–1616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Mei X, Chen YS, Chen FR, Xi SY, Chen ZP (2017) Glioblastoma stem cell differentiation into endothelial cells evidenced through live-cell imaging. Neuro-Oncology 19:1109–1118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Mischinger J, Frohlich E, Mannweiter S, Meindl C, Absenger-Novak M, Hutterer JC, Seles M, Augustin H, Chromecki TF, Jesche-Chromercki J, Pummer K, Zigeuner R (2019) Prognostic value of B7-H3 and the stage, size, grade and necrosis (SSIGN) score in metastatic clear cell renal cell carcinoma. Cent European J Urol 72:23–31

    PubMed  PubMed Central  CAS  Google Scholar 

  115. Moschetta M, Mishima Y, Kawano Y, Manier S, Paiva B, Palomera L, Aliawai Y, Calcinotto A, Unitt C, Sahin I, Sacco A, Glavey S, Shi J, Reagan MR, Prosper F, Bellone M, Chesi M, Bergsagel LP, Vacca A, Roccaro AM, Ghobrial IM (2016) Targeting vasculogenesis to prevent progression in multiple myeloma. Leukemia 30:1103–1115

    Article  CAS  PubMed  Google Scholar 

  116. Naito H, Kidoya H, Sakimoto S, Wakabayashi T, Takakura N (2012) Identification and characterization of a resident vascular stem/progenitor cell population in preexisting blood vessels. EMBO J 31:842–855

    Article  CAS  PubMed  Google Scholar 

  117. Naito H, Wakabayashi T, Kidoya H, Muramatsu F, Fakara K, Eino D, Yamane K, Iba T, Takakura N (2016) Endothelial side population cells contribute to tumor angiogenesis and antiangiogenic drug resistance. Cancer Res 76:3200–3210

    Article  CAS  PubMed  Google Scholar 

  118. Ngalia J, Green AR (2017) Myeloproliferative neoplasms: from origins to outcomes. Blood 130:2475–2483

    Article  CAS  Google Scholar 

  119. Nguyen-Kim TD, Frauenfelder T, Strobel K, Veit-Haibach P, Hueliner MW (2015) Assessment of bronchial and pulmonary blood supply in non-small cell lung cancer subtypes using computed tomography perfusion. Investig Radiol 50:179–186

    Article  Google Scholar 

  120. Nishimura R, Nishiwaki T, Kawasaki T, Sekine A, Suda R, Urushibara T, Suzuki T, Takayanagi S, Terada J, Sakao S, Tatsumi K (2015) Hypoxia-induced proliferation of tissue-resident endothelial progenitor cells in the lung. Am J Physiol Lung Cell Mol Physiol 308: L746–L758

    Google Scholar 

  121. Obad N, Espedal H, Jirik R, Sakariassen PO, Brekke Rygh C, Lund-Johansen M, Taxt T, Niclou SAP, Bjervig R, Keunen O (2018) Lack of functional normalization of tumour vessels following anti-angiogenic therapy in glioblastoma. J Cerebr Blood Flow Metab 38:1741–1753

    Article  Google Scholar 

  122. Ohga N, Ishikawa S, Maishi N, Akiyama K, Hida Y, Kawamoto T, Sadamoto Y, Osawa T, Yamamaoto K, Kondoh M (2012) Heterogeneity of tumor endothelial cells: comparison between tumor endothelial cells isolated from high- and low-metastatic tumors. Am J Pathol 180:1294–1307

    Article  CAS  PubMed  Google Scholar 

  123. Ohle SJ, Anandaiah A, Fabian AJ, Fine A, Kotton DN (2012) Maintenance and repair of the lung endothelium does not involve contributions from marrow-derived endothelial precursor cells. Am J Respir Cell Mol Biol 47:11–19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Ottesbach K (2019) Endothelial-to-haematopoietic transition: an update on the process of making blood. Biochem Soc Trans 47:2752–2760

    Google Scholar 

  125. Overman J, Fontaine F, Moustaqil M, Mittal D, Sierecki E, Sacilotto N, Zuegg J, Robertson AA, Holmes K, Salim AA, Mamidyala S, Butler MS, Robinson AS, Lesieur E, Johnston W, Alexandrov K, Black BL, Hogan BM, De Val S, Capon RJ, Carroll JS, Bailey TL, Koopman P, Jauch SMJ, Cooper MA, Gambin Y, Francois M (2017) Pharmacological targeting of the transcription factor SOX18 delays breast cancer in mice. elife 6:e21221

    Article  PubMed  PubMed Central  Google Scholar 

  126. Pàez-Ribes M, Allen E, Hudock J, Takedaq 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  127. Palomero J, Vegliante MC, Rodriguez ML, Equileor A, Castellano G, Planas-Rigol E, Jares P, Ribera-Cortada I, Cide MC, Campo E, Amador V (2014) SOX11 promotes tumor angiogenesis through transcriptional regulation of PDGFA in mantle cell lymphoma. Blood 124:2235–2247

    Article  CAS  PubMed  Google Scholar 

  128. Passalidou E, Trivella M, Singh N, Ferguson M, Hu J, Cesario A, Granone P, Nicholson AG, Goldstraw P, Ratcliffe C, Teflow M, Leigh I, Harris AL, Gatter KC, Pezzella F (2002) Vascular phenotype in angiogenic and non-angiogenic lung non-small cell carcinomas. Br J Cancer 88:244–249

    Article  Google Scholar 

  129. Pastushenko I, Van den Eynden GG, Vicente-Arregui S, Prieto-Torres L, Alvarez-Alegret R, Querol I, Dirix LY, Carapeto FJ, Vermeulen PB, Van Laere SJ (2016) Increased angiogenesis and lymphangiogenesis in metastatic sentinel lymph nodes is associated with nonsentinel lymph node and distant metastasis in patients with melanoma. Am J Dermapathol 38:338–346

    Article  Google Scholar 

  130. Patel J, Seppanen EJ, Rodero MP, Wong HY, Donovan P, Neufeld Z, Fisk NM, Francois M, Khosrotehrani (2017a) Functional definition of progenitors versus mature endothelial cells reveals key SoxF-dependent differentiation process. Circulation 135:786–805

    Article  CAS  PubMed  Google Scholar 

  131. Patel SI, Sanjana NE, Kishton RI, Eidizadeh A, Vodnala SK, Lee AH, Cam M, Gartner JJ, Jia L, Steinberg SM, Yamamoto TN, Merchant AS, Mehta GU, Chichura A, AShaslem O, Tran E, Eil R, Sukumar M, Guijarro EP, Day CP, Robbins P, Feldman S, Merlino G, Zhang F, Restifo NP (2017b) Identification of essential genes for cancer immunotherapy. Nature 548:537–542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Pervoliotis K, Ntellas P, Dadouli K, Koutoukoglou P, Ioannou M, Tepetes K (2017) Microvessel density in patients with cutaneous melanoma: an up-to-date systematic review and meta-analysis. J Skin Cancer 2017:2049140

    Google Scholar 

  133. Petrakis G, Veloza L, Clot G, Gine E, Gonzalez-Farre B, Navarro A, Bea S, Martinez A, Lopez-Guillermo A, Amador V, Ribera-Cortada I, Campo E (2019) Increased tumor angiogenesis in SOX11-positive mantle cell lymphoma. Histopathology in Press 75(5):704–714

    Article  Google Scholar 

  134. Pezzella F, Pastorino U, Tagliabue E, Andreola S, Sozzi G, Gasparini G, Menard S, Gatter KC, Harris AL, Fox S, Buyse M, Pilotti S, Pierotti M, Rilke F (1997) Non-small-cell lung carcinoma tumor growth without morphological evidence of neo-angiogenesis. Am J Pathol 151:1417–1423

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Piaggio G, Rosti V, Corselli M, Bertolotti F, Bergamaschi G, Pozzi S, Imperiale D, Chiavarina B, Bonetti E, Novara F, Sessarego M, Villani L, Garuti A, Massa M, Ghio R, Campanelli R, Bacigalupo A, Pecci A, Viarengo G, Zuffardi O, Frassoni F, Barosi G (2009) Endothelial colony-forming cells from patients with chronic myeloproliferative disorders lack the disease-specific molecular clonality marker. Blood 114:3127–3130

    Article  CAS  PubMed  Google Scholar 

  136. Picarda E, Ohaegbulam KC, Zang X (2016) Molecular pathways: targeting B7-H3 (CD276) for human cancer immunotherapy. Cancer Res 22:1–7

    Google Scholar 

  137. Porcù E, Maule F, Boso D, Rampazzo E, Barbieri V, Zuccolotto G, Rosato A, Frasson C, Viola G, Della Puppa A, Basso G, Persano L (2018) BMP9 counteracts the tumorigenic and pro-angiogenic potential of glioblastoma. Cell Death Differ 25:1808–1822

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  138. Pour L, Efebera Y, Granell M, Hajek R, Oriol A, Delaunay J, Le Du K, Eveillard JM, Karlin L; Maisnar V, Martinez-Lopez J, Mateos MV, Moreb J, Ribrag V, Richardson PG, Straub J, Byrne C, Jacques C, Zubair H, Oclo EM (2019) A phase 1 / 2 study of safety of safety and efficacy of melflufen and dexamethasone in combination with either bortezomib or daramutamamb in patients with RRMM; first report on phase 1 data. AACR annual meeting, Atlanta, 2019, abstract, CT080

    Google Scholar 

  139. Rajikumar SV, Mesa RA, Fonseca R, Schroeder G, Plevak MF, Diuspenzieri A, Lacy MQ, Lust JA, Witzig TE, Gertz MA, Kyle RA, Russell SJ, Greipp PR (2002) Bone marrow angiogenesis in 400 patients with monoclonal gammopathy of undetermined significance, multiple myeloma, and primary amyloidosis. Clin Cancer Res 8:2210–2216

    Google Scholar 

  140. Reardon DA, Lassman AB, Schiff D, Yunns SA, Gerstner ER, Choughesy TF, Lee EQ, Gaffey SC, Barns J, Bruno J, Murikansky A, Duda DG, Jain RK, When PY (2018) Phase 2 and biomarker study of trebanabib, an angiopoietin-blocking peptidobody, with and without bevacizumab for patients with recurrent glioblastoma. Cancer 124:1438–1448

    Article  CAS  PubMed  Google Scholar 

  141. Ribatti D, Vacca A (2018) New insights in anti-angiogenesis in multiple myeloma. Int J Mol Sci 19: 20131

    Google Scholar 

  142. Ribatti D, Annese T, Ruggieri S, Tamma R, Crivellato E (2019) Limitations of anti-angiogenic treatment of tumors. Trans Oncol 12:981–986

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  144. Richardson P, Ocio E, Oriol A, Larocca A, Rodriguez Otero P, Moreb J, Bladé J, Hassoun H, Cavo M, Alegre A, Mazumder A, Maisel C, Paner A, Gabrail N, Zonder JA, Chauhan D, Harmenberg J, Thuresson S, Zut A, Mateos MV (2019) OP-106 Horizon – Melflufen therapy for RRMM patients refractory to Daratumumab and /or pomalidomide; updated results and first report on PFS. Blood 132:600

    Article  Google Scholar 

  145. Rini RI, Powles T, Atkins MB, Escudier B, DE MD, Suarez C, Bracarda S, Stadier WM, Donskov E, Lee JL, Hawkins R, Ravaud A, Aleskeev B, Staehler M, uemura M, De Giorgi U, Mellado B, Porta C, Melichar B, Gurney H, Bedke J, Choueri TK, Parnis F, Khaznadar T, Thobhani A, LI S, Piault-Louis E, FrantzG HM, Schiff C, Green MC, Motzer RJ, IMmotion151 Study Group (2019) Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion 151): a multicenter, open-label, phase 3, randomized controlled trial. Lancet 393:2404–2415

    Article  PubMed  Google Scholar 

  146. Rocha R, Torres A, Ojeda K, Uribe D, Rocha D, Erices J, Niechi I, Ehrenfeld P, San Martin R, Quezada C (2018) The adenosine A3 receptor regulates differentiation of glioblastoma stem-like cells to endothelial cells under hypoxia. Int J Mol Sci 19:1228

    Article  PubMed Central  CAS  Google Scholar 

  147. Rosti V, Villani L, Riboni R, Poletto V, Bonetti F, Tozzi L, Bergamaschi G, Catarsi P, Dallera E, Novara F (2013) Spleen endothelial cells from patients with myelofibrosis harbor the JAK2V617F mutation. Blood 121:360–368

    Article  CAS  PubMed  Google Scholar 

  148. Saltarella I, Frassanito MA, Lamanuzzi A, Brevi A, Leone P, Desantis V, Di Marzo L, Bellone M, Derudas D, Ribatti D, Chiaramonte R, Palano MT, Neri A, Mariggiò MA, Fumarulo R, Dammacco F, Recanelli V, Vacca A, Ria R (2019) Homotypic and heterotypic activation of the Notch pathway in multiple myeloma-enhanced angiogenesis: a novel therapeutic target? Neoplasia 21:93–105

    Article  CAS  PubMed  Google Scholar 

  149. Sattiraju A, Mintz A (2019) Pericytes in glioblastomas: multifaceted role within tumor microenvironments and potential for therapeutic interventions. Adv Exp Med Biol 1147: 65–91

    Google Scholar 

  150. Schmitt CE, Woolls MJ, Jin SW (2013) Mutant-specific gene expression profiling identifies SRY-related HMG box 11b (SOX11b) as a novel regulator of vascular development in zebrafish. Mol Cells 35:166–172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Schneller D, Hofer-Warbinek R, Sturtzel C, Lipnik K, Gencelli B, Seltenhammer M, Wen M, Testori J, Bilban M, Borowski A, Windwarder M, Kapel SS, Besemfelder E, Cejka P, Habertheuer A, Schlechta B, Majdic O, Altmann F, Kocher A, Augustin HG, Luttmann W, Hofer E (2019) Cytokine-like 1 is a novel proangiogenic factor secreted by and mediating functions of endothelial progenitor cells. Circ Res 124:243–255

    Article  CAS  PubMed  Google Scholar 

  152. Scholz A, Harter PN, Cremer S, Yalcin BH, Gurnik S, Yamaii M, Di Tacchio M, Sommer K, Baumgarten P, Bahr O, Steinbach JP, Trojan J, Glas M, Herlinger U, Krex D, Meinhardt M, Weyerbrock A, Timmer M, Goldbrunner R, Deckert M, Braun C, Schittenhelm J, Frueh JT, Ulrich E, Mittelbronn M, Plate KH, Reiss Y (2016) Endothelial cell-derived angiopoietin-2 is a therapeutic target in treatment-naïve and bevacizumab-resistant glioblastoma. EMBO Mol Med 8:39–57

    Article  CAS  PubMed  Google Scholar 

  153. Seaman S, Stevens J, Yang MY, Logsdon D, Graff-Cheny C, Croix B (2007) Genes that distinguish physiological and pathological angiogenesis. Cancer Cell 11:539–554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Seaman S, Zhu Z, Saha S, Zhang XM, Yang MY, Hilton MB, Morris K, Szot C, Morris H, Swing DA, Tessarollo L, Smith SW, Degrado S, Borkin D, Jain N, Scheiermann J, Feng Y, Wang Y, Li J, Welsch D, DeCrescenzo D, Chaudhary A, Zudaire E, Klarmann KD, Keller JR, Dimitrov DS, Croix B (2017) Eradication of tumors through simultaneous ablation of CD276/B7-H3-positive tumor cells and tumor vasculature. Cancer Cell 31:515.e8

    Article  CAS  Google Scholar 

  155. Sekine A, Nishiwaki T, Nishimura R, Kawasaki T, Urushibara T, Suda R, Suzuki T, Takayanagi S, Terada J, Sakao S, Tada Y, Iwama A, Tatsumi K (2016) Prominin-1/CD133 expression as potential tissue-resident vascular endothelial progenitor cells in the pulmonary circulation. Am J Physiol Lung Cell Mol Biol Physiol 310:L1130–L1142

    Article  Google Scholar 

  156. Singhal M, Liu X, Inverse D, Jiang K, Dai J, He H, Bartels S, Li W, Pari AAA, Gengenbacher N, Besemfelder E, Hui L, Augustin HG, Hu J (2018) Endothelial cell fitness dictates the source of regenerating liver vasculature. J Exp Med 215:2497–2508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Son YS, Kwon SM, Cho JY (2019) CD276 (B7-H3) maintains proliferation and regulates differentiation in angiogenic function in late endothelial progenitor cells. Stem Cells 37:382–394

    Article  CAS  PubMed  Google Scholar 

  159. Souweidane MM, Kramer K, Pendit-Taskar N, Zhou Z, Haque S, Zanzonico P, Carrasquillo JA, Lyashchenko SK, Takur SB, Donzelli M, Turner RS, Lewis JS, Cheung NV, Larson SM, Dunkel IJ (2018) Convection-enhanced delivery for diffuse intrinsic pontine glioma: a single-centre, dose-escalation, phase 1 trial. Lancet Oncol 19:1040–1050

    Article  PubMed  PubMed Central  Google Scholar 

  160. Sozer S, Fiel MI, Schiano T, Xu M, Mascarenhas J, Hoffman R (2009a) The presence of JAK2V617F mutation in the liver endothelial cells of patients with Budd-Chiari syndrome. Blood 113:5246–5249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Sozer S, Ishii T, Fiel MI, Wang J, Wang X, Zhang W, Godbold J, Xu M, Hoffman R (2009b) Human CD34+ cells are capable of generating normal and JAK2V617F positive endothelial like cells in vivo. Blood Cells Mol Dis 43:304–312

    Article  CAS  PubMed  Google Scholar 

  162. Strese S, Wickstrom M, Fuchs PF, Fryknas M, Gerwins P, Dale T, Larsson R, Guilbo J (2013) The novel alkylating prodrug melflufen (J1) inhibits angiogenesis in vitro and in vivo. Biochem Pharmacol 86:888–895

    Article  CAS  PubMed  Google Scholar 

  163. Streubel B, Chott A, Huber D, Exner M, Jager U, Wagner O, Schwarzinger I (2004) Lymphoma-specific genetic aberrations in microvascular endothelial cells in B-cell lymphomas. N Engl J Med 351:250–259

    Article  CAS  PubMed  Google Scholar 

  164. Sturtzel C, Lipnik K, Hofer-Warbinek R, Tsetori J, Ebner B, Seigner J, Qiu P, Bilban M, Jandrositz A, Preisegger KH, Untergasser G, Gunsilius E, de Martin R, Kroll J, Hofer E (2018) FOXF1 mediates endothelila progenitor functions and regulates vascular sprouting. Front Bioeng Biotec 6:76

    Article  Google Scholar 

  165. Su C, Zhao Y, Shi J, Zhang J, Yuan Y, Gu Y, Zhang F, Gao X, Wang C, Wang Y, Wang Z, Hu P, Qin J, Xiao L, Chang T, Wang L, Xi Y, Yin H, Chen H, Zhang L, Cheng G, Lin J, Zhang MM, Li Z, Ye J (2019) Isocitrate dehydrogenase 1 mutation reduces the pericyte coverage of microvessels in astrocytic tumors. J Neuroncol 143: 187–196

    Google Scholar 

  166. Suzuki T, Tada Y, Nishimura R, Kawasaki T, Sekine A, Urushibara T, Kato F, Kinoshita T, Ikari J, West J, Tatsumi K (2016) Endothelial-to-mesenchymal transition in lipopolysaccharide-induced acute lung injury drives a progenitor cell-like phenotype. Am J Physiol Lung Cell Mol Physiol 310:L1185–L1190

    Article  PubMed  Google Scholar 

  167. Tabouret E, Tchoghandjian A, Denicolai E, Delfino C, Metellus P, Graillon T, Boucard C, Nanni I, Padovani L, Ouafik L, Figarella-Branger D, Chinot O (2015) Recurrence of glioblastoma after radio-chemotherapy is associated with an angiogenic switch to the CXCL12-CXCR4 pathway. Oncotarget 6:11664–11675

    Article  PubMed  PubMed Central  Google Scholar 

  168. Teofili L, Martini M, Iachininoto MG, Capodimonti S, Nuzzolo ER, Torti L, Cenci T, Larocca LM, Leone G (2011) Endothelial progenitor cells are clonal and exhibit the JAK2(V617F) mutation in a subset of thrombotic patients with Ph-negative myeloproliferative neoplasms. Blood 117:2700–2707

    Article  CAS  PubMed  Google Scholar 

  169. Testa U, Saulle E, Castelli G, Pelosi E (2016) Endothelial progenitor cells in hematologic malignancies. Stem Cell Invest 3:26

    Article  Google Scholar 

  170. Tian L, Goldstein A, Wang H, Ching Lo H, Sun Kim I, Welte T, Sheng K, Dobroiecki LE, Zhang X, Putiuri N, Phung TL, Mani SA, Stossi F, Streekumar A, Mancini MA, Decker WK, Zong C, Lewis MT, Zhang KH (2017) Mutual regulation of tumor vessel normalization and immunostimulatory reprogramming. Nature 544:250–254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Tura O, Skinner EM, Barclay GR, Sannel K, Gallagheer RC, Brittan M (2013) Late outgrowth endothelial cells resemble mature endothelial cells and are not derived from bone marrow. Stem Cells 31:338–348

    Article  CAS  PubMed  Google Scholar 

  172. Tzankov A, Heiss S, Ebner S, Sterlacci W, Schaefer G, Augustin F, Fiegl M, Dirnhofer S (2007) Angiogenesis in nodal B cell lymphomas: a high throughput study. J Clin Pathol 60:476–482

    Article  CAS  PubMed  Google Scholar 

  173. Uribesalgo I, Hoffmann D, Zhang Y, Kavirayani A, Lazovic J, Berta J, Navatchkova M, Pai TP, Wimmer RA, Lazlo V, Schramek D, Karim R, Tortola L, Deswal S, Haas L, Zuber J, Szucs M, Kuba K, Dome B, Cao Y, Haubner BJ, Penninger JM (2019) Apelin inhibition prevents resistance and metastasis associated with anti-angiogenic therapy. EMBO Mol Med 11:e9266

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  174. Vacca A, Ribatti D (2006) Bone marrow angiogenesis in multiple myeloma. Leukemia 20:193–199

    Article  CAS  PubMed  Google Scholar 

  175. Vacca A, Ria R, Semeraro F, Merchionne F, Coluccia M, Boccarelli A, Scavelli C, Nico B, Gernone A, Battelli F, Tabilio A, Guidolin D, Petrucci MT, Ribatti D, Dammacco F (2003) Endothelial cells in the bone marrow of patients with multiple myeloma. Blood 102:3340–3348

    Article  CAS  PubMed  Google Scholar 

  176. Vainchenker W, Kralovics R (2017) Genetic basis and molecular pathophysiology of classical myeloproliferative neoplesms. Blood 130:2475–2483

    Article  CAS  Google Scholar 

  177. Vajkoczy P, Blum S, Lamparter M, Mailhammer R, Erber R, Engelhardt B, Vestweber D, Hatzopoulos AK (2003) Multistep nature of microvascular recruitment of ex vivo-expanded embryonic endothelial progenitor cells during tumor angiogenesis. J Exp Med 197:1755–1765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Vessela P, Tonar Z, Salek D, Vokurka S, Trneny M, Kodet R, Moulis M, Kasparova P, Vermerova Z, Valenska Z, Strilesky J, Michal M, Boudova L (2014) Microvessel density of mantle cell lymphoma. A retrospective study of its prognostic role and the correlation with the Ki-67 and the mantle cell lymphoma international prognostic index in 177 cases. Virchows Arch 465:587–597

    Article  CAS  Google Scholar 

  179. Voutouri C, Kirkpatrick ND, Chung E, Mpekris F, Baish JW, Munn LL, Fukumura D, Stylianopoulos T, Jain RK (2019) Experimental and computational analyses reveal dynamics of tumor vessel cooption and optimal treatment strategies. Proc Natl Acad Sci USA 116:2662–2671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Wakabayashi T, Naito H, Suehiro JI, Lin Y, Kawaji H, Iba T, Kouno T, Ishikawa-Kato S, Furuno M, Takara K, Maramatsu F, Weizhen J, Kidoya H, Ishihara K, Hayashizaki Y, Nishida K, Yoder MC, Takakura N (2018) CD157 marks tissue-resident endothelial stem cells with homeostatic and regenerative properties. Cell Stem Cell 22:384–397

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  182. Wang P, Du H, Zhou CC, Song J, Liu X, Cao X, Mehta JL, Shi Y, Su DF, Miao CY (2014) Intracellular NAMPT-NAD+-SIRT1 cascade improves post-ischaemic vascular repair by modulating Notch signaling in endothelial progenitors. Cardiovasc Res 104:477–488

    Article  CAS  PubMed  Google Scholar 

  183. Wang X, Guo G, Guan H, Yu Y, Lu J, Yu T (2019) Challenges and potential of PD-1/PD-L1 checkpoint blockade immunotherapy for glioblastoma. J Expo Clin Cancer Res 38:87

    Article  Google Scholar 

  184. Weis SM, Cheresh DA (2011) Tumor angiogenesis: molecular pathways and therapeutic targets. Nature Med 17:1359–1369

    Article  CAS  PubMed  Google Scholar 

  185. Wilson KE, Bachawal SV, Abou-Elkacem L, Jensen K, Machtaler S, Tian L, Willmann JK (2017) Spectroscopic photoacoustic molecular imaging of breast cancer using a B7-H3-targeted ICG contrast agent. Theranotics 7:1463–1476

    Article  CAS  Google Scholar 

  186. Xian X, Sakurai T, Kamoyoshi A, Ichikawa-Shindo Y, Tanaka M, Koyama T, Kawate H, Yang L, Liu T, Imai A, Zhai L, Hirabayashi K, Dai K, Tanimura K, Liu T, Cui N, Igarashi K, Yamauchi A, Shindo T (2017) Vasoprotective activities of the adrenomedullin-RAMP2 system in endothelial cells. Endocrinology 158:1359–1372

    Article  CAS  PubMed  Google Scholar 

  187. Xie M, Liu M, He CS (2012) SIRT1 regulates endothelial Notch signaling in lung cancer. PLoS One 7:e45331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Xu Y, Sun P, Wang JY, Li ZZ, Gao RL, Wang XZ, Phillips WD, Liang SX (2019) Differentiation of CD45/CD31+ lung side population cells into endothelial and smooth muscle cells in vitro. Int J Mol Med 43:1128–1138

    CAS  PubMed  PubMed Central  Google Scholar 

  189. Xue W, Du X, Wu H, Liu H, Xie T, Tong H, Chen X, Guo Y, Zhang W (2017) Aberrant glioblastoma neovascularization patterns and their correlation with DCE-MRI-derived parameters following temozolamide and bevacizumab treatment. Sci Rep 7:13894

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  190. Yang SB, Gao KD, Jiang T, Cheng SJ, Li WB (2017) Bevacizumab combined with chemotherapy for glioblastoma: a meta-analysis of randomized controlled trials. Oncotarget 8:57337–57344

    Article  PubMed  PubMed Central  Google Scholar 

  191. Yeh HS, Chen H, Manvak SJ, Swift RA, Campbell RA, Wang C, Li M, Waterman G, Gordon MS, Ma J, Bonavida B, Berenson JR (2006) Serum pleiotrophin levels are elevated in multiple myeloma patients and correlate with disease status. Br J Haematol 133:5426–5529

    Article  CAS  Google Scholar 

  192. Yuan X, Zhang J, Ao G, Quan C, Tian Y, Li H (2012) Lung cancer perfusion: can we measure pulmonary and bronchial circulation simultaneously? Eur Radiol 22:1665–1671

    Article  PubMed  Google Scholar 

  193. Yurugi-Kobayashi T, Itoh H, Scroeder T, Nakano A, Narazaki G, Kita F, Yanagi K, Hiraoka-Kanie M, Inoue E, Ara T, Nagasawa T, Just U, Nakao K, Nishikawa S, Yamashita JK (2006) Adrenomedullin/cyclic AMP pathway induces Notch activation and differentiation of arterial endothelial cells from vascular progenitors. Arterioscler Thromb Vasc Biol 26:1977–1984

    Article  CAS  PubMed  Google Scholar 

  194. Zeng Q, Li S, Chepeha DB, Giordano TJ, Li J, Zhang H, Polverini PJ, Nor J, Kitajewski J, Wang CY (2005) Crosstalk between tumor and endothelial cells promotes tumor angiogenesis by MAPK activation of Notch signaling. Cancer Cell 8:13–23

    Article  CAS  PubMed  Google Scholar 

  195. Zhan H, Lin CH, Segal Y, Kaushansky K (2018) The JAK2V617F-bearing vascular niche promotes clonal expansion in myeloproliferative neoplasms. Leukemia 32:462–469

    Article  CAS  PubMed  Google Scholar 

  196. Zhang H, Vakil V, Braunstein M, Smith EL, Maroney J, Chen L, Dai K, Berenson JR, Hussain MM, Klueppelberg U, Norin AJ, Akman HO, Oczelik T, Batuman OA (2005) Circulating endothelial progenitor cells in multiple myeloma: implications and significance. Blood 105:3266–3294

    Google Scholar 

  197. Zhang X, Sullivan PS, Soslow RA, Waitz R, Reuter VE, Wilton A, Thaler HT, Arul M, Slovin SF, Wei J, Spriggs DR, Dupont J, Allkison JP (2010) Tumor associated endothelial expression of B7-H3 predicts survival in ovarian carcinomas. Mod Pathol 23:1104–1112

    Article  CAS  Google Scholar 

  198. Zhao O, Gomez GA, Zhao Y, Yang Y, Cao D, Lu J, Yang H, Lin S (2018) ETV2 mediates endothelial transdifferentiation of glioblastoma. Sign Trans Target Ther 3:4

    Article  CAS  Google Scholar 

  199. Zhou W, Chen C, Shi Y, Wu Q, Gimple RC, Fang X, Huang Z, Zhai K, Ke SQ, Ping YF, Feng H, Rich JN, YU JS, Bao S, Bian XW (2017) Targeting glioma stem cell-derived pericytes disrupts the blood-tumor barrier and improves chemotherapeutic efficacy. Cell Stem Cell 21:591–603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Zhou Y, Zhao M, Du Y, Liu Y, Zhao G, Ye L, Li Q, Li H, Wang X, Liu X, Guo Y, Liu J, Huang Y (2019) MicroRNA-195 suppresses the progression of lung adenocarcinoma by directly targeting apelin. Torac Cancer 10:1419–1430

    CAS  Google Scholar 

  201. Zuazo-Gatzelu I, Casanovas O (2018) Unraveling the role of angiogenesis in cancer ecosystems. Front Oncol 8:248

    Article  Google Scholar 

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Testa, U., Pelosi, E., Castelli, G. (2020). Endothelial Progenitors in the Tumor Microenvironment. In: Birbrair, A. (eds) Tumor Microenvironment. Advances in Experimental Medicine and Biology, vol 1263. Springer, Cham. https://doi.org/10.1007/978-3-030-44518-8_7

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