Progress in detecting cell-surface protein receptors: The erythropoietin receptor example

Annals of Hematology

Volumn 93, Issue 2, 2014, Pages 181-192

  Elliott, Steve ^a   Sinclair, Angus ^a   Collins, Helen ^a,c   Rice, Linda ^a   Jelkmann, Wolfgang ^b  

^a AMGEN INC   (United States)

^b UNIVERSITY OF LÜBECK   (Germany)

^c GILEAD SCIENCES   (United States)

Author keywords

Angiogenesis; Antibody; Cancer; Erythropoiesis; Erythropoietin receptor

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR 2; ERBB2 PROTEIN, HUMAN; ERYTHROPOIETIN RECEPTOR;

ANIMAL; BIOSYNTHESIS; BONE MARROW; CYTOLOGY; ERYTHROID CELL; GENE EXPRESSION REGULATION; GENETICS; HUMAN; IMMUNOHISTOCHEMISTRY; METABOLISM; NORTHERN BLOTTING; PHYSIOLOGY; PROCEDURES; WESTERN BLOTTING;

ANIMALS; BLOTTING, NORTHERN; BLOTTING, WESTERN; BONE MARROW; ERYTHROID CELLS; GENE EXPRESSION REGULATION; HUMANS; IMMUNOHISTOCHEMISTRY; RECEPTOR, ERBB-2; RECEPTORS, ERYTHROPOIETIN;

EID: 84895057844     PISSN: 09395555     EISSN: 14320584     Source Type: Journal    
DOI: 10.1007/s00277-013-1947-2     Document Type: Review

References (94)

1. Allegra CJ, Jessup JM, Somerfield MR, Hamilton SR, Hammond EH, Hayes DF, McAllister PK, Morton RF, Schilsky RL (2009) American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol 27(12):2091-2096. doi: 10.1200/JCO.2009.21.9170
2. Cobleigh MA, Vogel CL, Tripathy D, Robert NJ, Scholl S, Fehrenbacher L, Wolter JM, Paton V, Shak S, Lieberman G, Slamon DJ (1999) Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 17(9):2639-2648
3. Paik S, Bryant J, Tan-Chiu E, Romond E, Hiller W, Park K, Brown A, Yothers G, Anderson S, Smith R, Wickerham DL, Wolmark N (2002) Real-world performance of HER2 testing - National Surgical Adjuvant Breast and Bowel Project experience. J Natl Cancer Inst 94(11):852-854
4. Perez EA, Suman VJ, Davidson NE, Martino S, Kaufman PA, Lingle WL, Flynn PJ, Ingle JN, Visscher D, Jenkins RB (2006) HER2 testing by local, central, and reference laboratories in specimens from the North Central Cancer Treatment Group N9831 intergroup adjuvant trial. J Clin Oncol 24(19):3032-3038. doi: 10.1200/JCO.2005.03.4744
5. Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med 131(1):18-43. doi: 10.1043/1543-2165(2007)131[18:ASOCCO]2.0.CO;2
6. Elliott S, Sinclair AM (2012) The effect of erythropoietin on normal and neoplastic cells. Biologics: Targets and Therapy 6:163-189
7. Amgen Inc. (2011) Aranesp® (Darbepoetin alfa) prescribing information. Amgen Inc., Thousand Oaks
8. Henke M, Mattern D, Pepe M, Bezay C, Weissenberger C, Werner M, Pajonk F (2006) Do erythropoietin receptors on cancer cells explain unexpected clinical findings? J Clin Oncol 24(29):4708-4713
9. Osterborg A, Aapro M, Cornes P, Haselbeck A, Hayward CR, Jelkmann W (2007) Preclinical studies of erythropoietin receptor expression in tumour cells: impact on clinical use of erythropoietic proteins to correct cancer-related anaemia. Eur J Cancer 43(3):510-519
10. Ribatti D (2010) Erythropoietin and tumor angiogenesis. Stem Cells Dev 19(1):1-4
11. Suzuki N, Ohneda O, Takahashi S, Higuchi M, Mukai HY, Nakahata T, Imagawa S, Yamamoto M (2002) Erythroid-specific expression of the erythropoietin receptor rescued its null mutant mice from lethality. Blood 100(7):2279-2288
12. Elliott S, Busse L, McCaffery I, Rossi J, Sinclair A, Spahr C, Swift S, Begley CG (2010) Identification of a sensitive anti-erythropoietin receptor monoclonal antibody allows detection of low levels of EpoR in cells. J Immunol Methods 352(1-2):126-139
13. Sinclair AM, Coxon A, McCaffery I, Kaufman S, Paweletz K, Liu L, Busse L, Swift S, Elliott S, Begley CG (2010) Functional erythropoietin receptor is undetectable in endothelial, cardiac, neuronal, and renal cells. Blood 115:4264-4272
14. Elliott S, Swift S, Busse L, Scully S, Van G, Rossi J, Johnson C (2013) Epo receptors are not detectable in primary human tumor tissue samples. PLoS One 8(7):e68083
15. Bordeaux J, Welsh A, Agarwal S, Killiam E, Baquero M, Hanna J, Anagnostou V, Rimm D (2010) Antibody validation. Biotechniques 48(3):197-209
16. Elliott S, Busse L, Bass MB, Lu H, Sarosi I, Sinclair AM, Spahr C, Um M, Van G, Begley CG (2006) Anti-Epo receptor antibodies do not predict Epo receptor expression. Blood 107(5):1892-1895
17. Kirkeby A, van Beek J, Nielsen J, Leist M, Helboe L (2007) Functional and immunochemical characterisation of different antibodies against the erythropoietin receptor. J Neurosci Methods 164(1):50-58
18. Laugsch M, Metzen E, Svensson T, Depping R, Jelkmann W (2008) Lack of functional erythropoietin receptors of cancer cell lines. Int J Cancer 122(5):1005-1011
19. Miller CP, Lowe KA, Valliant-Saunders K, Kaiser JF, Mattern D, Urban N, Henke M, Blau CA (2009) Evaluating erythropoietin-associated tumor progression using archival tissues from a phase III clinical trial. Stem Cells 27(9):2353-2361
20. Weinstein PR, Hong S, Sharp FR (2004) Molecular identification of the ischemic penumbra. Stroke 35(11 Suppl 1):2666-2670. doi: 10.1161/01.STR. 0000144052.10644.ed
21. Swift S, Ellison AR, Kassner P, McCaffery I, Rossi J, Sinclair AM, Begley CG, Elliott S (2010) Absence of functional EpoR expression in human tumor cell lines. Blood 115:4254-4263
22. Saintigny P, Besse B, Callard P, Vergnaud AC, Czernichow S, Colombat M, Girard P, Validire P, Breau JL, Bernaudin JF, Soria JC (2007) Erythropoietin and erythropoietin receptor coexpression is associated with poor survival in stage I non-small cell lung cancer. Clin Cancer Res 13(16):4825-4831
23. Lopez TV, Lappin TR, Maxwell P, Shi Z, Lopez-Marure R, Aguilar C, Rocha-Zavaleta L (2011) Autocrine/paracrine erythropoietin signalling promotes JAK/STAT-dependent proliferation of human cervical cancer cells. Int J Cancer 129(11):2566-2576. doi: 10.1002/ijc.25935
24. Palumbo C, Battisti S, Carbone D, Albonici L, Alimandi M, Bei R, Modesti A (2008) Recombinant erythropoietin differently affects proliferation of mesothelioma cells but not sensitivity to cisplatin and pemetrexed. Cancer Chemother Pharmacol 61(5):893-901
25. Yin D, Kawabata H, Tcherniamtchouk O, Huynh T, Black KL, Koeffler HP (2007) Glioblastoma multiforme cells: expression of erythropoietin receptor and response to erythropoietin. Int J Oncol 31(5):1193-1198
26. Elliott S, Busse L, Swift S, McCaffery I, Rossi J, Kassner P, Begley CG (2012) Lack of expression and function of erythropoietin receptors in the kidney. Nephrol Dial Transplant 27:2733-2745
27. Lin CS, Lim SK, D'Agati V, Costantini F (1996) Differential effects of an erythropoietin receptor gene disruption on primitive and definitive erythropoiesis. Genes Dev 10(2):154-164
28. Wu H, Liu X, Jaenisch R, Lodish HF (1995) Generation of committed erythroid BFU-E and CFU-E progenitors does not require erythropoietin or the erythropoietin receptor. Cell 83(1):59-67
29. Broudy VC, Lin N, Brice M, Nakamoto B, Papayannopoulou T (1991) Erythropoietin receptor characteristics on primary human erythroid cells. Blood 77(12):2583-2590
30. Zeigler BM, Vajdos J, Qin W, Loverro L, Niss K (2010) A mouse model for an erythropoietin-deficiency anemia. Dis Model Mech 3(11-12):763-772. doi: 10.1242/dmm.004788
31. Zon LI, Youssoufian H, Mather C, Lodish HF, Orkin SH (1991) Activation of the erythropoietin receptor promoter by transcription factor GATA-1. Proc Natl Acad Sci U S A 88(23):10638-10641
32. Kassouf MT, Hughes JR, Taylor S, McGowan SJ, Soneji S, Green AL, Vyas P, Porcher C (2010) Genome-wide identification of TAL1's functional targets: insights into its mechanisms of action in primary erythroid cells. Genome Res 20(8):1064-1083
33. D'Andrea AD, Fasman GD, Lodish HF (1989) Erythropoietin receptor and interleukin-2 receptor beta chain: a new receptor family. Cell 58(6):1023-1024
34. Jones SS, D'Andrea AD, Haines LL, Wong GG (1990) Human erythropoietin receptor: cloning, expression, and biologic characterization. Blood 76(1):31-35
35. Hilton DJ, Watowich SS, Murray PJ, Lodish HF (1995) Increased cell surface expression and enhanced folding in the endoplasmic reticulum of a mutant erythropoietin receptor. Proc Natl Acad Sci U S A 92(1):190-194
36. Neumann D, Wikstrom L, Watowich SS, Lodish HF (1993) Intermediates in degradation of the erythropoietin receptor accumulate and are degraded in lysosomes. J Biol Chem 268(18):13639-13649
37. Constantinescu SN, Ghaffari S, Lodish HF (1999) The erythropoietin receptor: structure, activation and intracellular signal transduction. Trends Endocrinol Metab 10(1):18-23
38. Huang LJ, Constantinescu SN, Lodish HF (2001) The N-terminal domain of Janus kinase 2 is required for Golgi processing and cell surface expression of erythropoietin receptor. Mol Cell 8(6):1327-1338
39. Narhi LO, Aoki KH, Philo JS, Arakawa T (1997) Changes in conformation and stability upon formation of complexes of erythropoietin (EPO) and soluble EPO receptor. J Protein Chem 16(3):213-225
40. Philo JS, Aoki KH, Arakawa T, Narhi LO, Wen J (1996) Dimerization of the extracellular domain of the erythropoietin (EPO) receptor by EPO: one high-affinity and one low-affinity interaction. Biochemistry 35(5):1681-1691
41. Syed RS, Reid SW, Li C, Cheetham JC, Aoki KH, Liu B, Zhan H, Osslund TD, Chirino AJ, Zhang J, Finer-Moore J, Elliott S, Sitney K, Katz BA, Matthews DJ, Wendoloski JJ, Egrie J, Stroud RM (1998) Efficiency of signalling through cytokine receptors depends critically on receptor orientation. Nature 395(6701):511-516
42. Watowich SS (1999) Activation of erythropoietin signaling by receptor dimerization. Int J Biochem Cell Biol 31(10):1075-1088
43. Remy I, Wilson IA, Michnick SW (1999) Erythropoietin receptor activation by a ligand-induced conformation change. Science 283(5404):990-993
44. Jelkmann W, Bohlius J, Hallek M, Sytkowski AJ (2008) The erythropoietin receptor in normal and cancer tissues. Crit Rev Oncol Hematol 67(1):39-61. doi: 10.1016/j.critrevonc.2008.03.006
45. Jegalian AG, Wu H (2002) Differential roles of SOCS family members in EpoR signal transduction. J Interferon Cytokine Res 22(8):853-860
46. Minoo P, Zadeh MM, Rottapel R, Lebrun JJ, Ali S (2004) A novel SHP-1/Grb2-dependent mechanism of negative regulation of cytokine-receptor signaling: contribution of SHP-1 C-terminal tyrosines in cytokine signaling. Blood 103(4):1398-1407
47. Sinclair AM, Rogers N, Busse L, Archibeque I, Brown W, Kassner PD, Watson JEV, Arnold GE, Nguyen KCQ, Powers S, Elliott S (2008) Erythropoietin receptor transcription is neither elevated nor predictive of surface expression in human tumour cells. Br J Cancer 98(6):1059-1067
48. Su AI, Wiltshire T, Batalov S, Lapp H, Ching KA, Block D, Zhang J, Soden R, Hayakawa M, Kreiman G, Cooke MP, Walker JR, Hogenesch JB (2004) A gene atlas of the mouse and human protein-encoding transcriptomes. Proc Natl Acad Sci U S A 101(16):6062-6067
49. Sinclair AM, Todd MD, Forsythe K, Knox SJ, Elliott S, Begley CG (2007) Expression and function of erythropoietin receptors in tumors: implications for the use of erythropoiesis-stimulating agents in cancer patients. Cancer 110(3):477-488
50. Volgger B, Kurz K, Zoschg K, Theurl I, Ciresa-Konig A, Marth C, Weiss G (2010) Importance of erythropoetin receptor expression in tumour tissue for the clinical course of breast cancer. Anticancer Res 30(9):3721-3726
51. Winter SC, Shah KA, Campo L, Turley H, Leek R, Corbridge RJ, Cox GJ, Harris AL (2005) Relation of erythropoietin and erythropoietin receptor expression to hypoxia and anemia in head and neck squamous cell carcinoma. Clin Cancer Res 11(21):7614-7620
52. vanZoelen EJ (1989) Receptor-ligand interaction: a new method for determining binding parameters without a priori assumptions on non-specific binding. Biochem J 262(2):549-556
53. Komatsu N, Yamamoto M, Fujita H, Miwa A, Hatake K, Endo T, Okano H, Katsube T, Fukumaki Y, Sassa S et al (1993) Establishment and characterization of an erythropoietin-dependent subline, UT-7/Epo, derived from human leukemia cell line, UT-7. Blood 82(2):456-464
54. Sawada K, Krantz SB, Sawyer ST, Civin CI (1988) Quantitation of specific binding of erythropoietin to human erythroid colony-forming cells. J Cell Physiol 137(2):337-345
55. Ohigashi T, Yoshioka K, Fisher JW (1996) Autocrine regulation of erythropoietin gene expression in human hepatocellular carcinoma cells. Life Sci 58(5):421-427
56. Gewirtz DA, Di X, Walker TD, Sawyer ST (2006) Erythropoietin fails to interfere with the antiproliferative and cytotoxic effects of antitumor drugs. Clin Cancer Res 12(7:Pt 1):2232-2238
57. Lester RD, Jo M, Campana WM, Gonias SL (2005) Erythropoietin promotes MCF-7 breast cancer cell migration by an ERK/mitogen-activated protein kinase-dependent pathway and is primarily responsible for the increase in migration observed in hypoxia. J Biol Chem 280(47):39273-39277
58. Datta SR, Brunet A, Greenberg ME (1999) Cellular survival: a play in three Akts. Genes Dev 13(22):2905-2927
59. Swift S, Elliott S, Sinclair A, Begley CG (2010) Erythropoietin receptor in ovarian cancer cells - letter. Mol Cancer Ther 9(4):1070-1071
60. Doan HQ, Bowen KA, Jackson LA, Evers BM (2009) Toll-like receptor 4 activation increases Akt phosphorylation in colon cancer cells. Anticancer Res 29(7):2473-2478
61. Hsu RY, Chan CH, Spicer JD, Rousseau MC, Giannias B, Rousseau S, Ferri LE (2011) LPS-induced TLR4 signaling in human colorectal cancer cells increases beta1 integrin-mediated cell adhesion and liver metastasis. Cancer Res 71(5):1989-1998
62. Sinclair A, Archibeque I, Zhan J, Liu L, Emkey R, Doherty E, Begley CG (2011) Potency and selectivity assessment of small molecules against Janus Kinase (JAK) 2: Widely used AG490 inhibitor is neither potent, nor selective for JAK2. Blood 118:Abstract 4780
63. Acs G, Acs P, Beckwith SM, Pitts RL, Clements E, Wong K, Verma A (2001) Erythropoietin and erythropoietin receptor expression in human cancer. Cancer Res 61(9):3561-3565
64. Kang JK, Chang CH, Nam HJ, Kim SK, Ahn KJ, Seok H, Park SJ, Kang YJ, Jo YS, Shong M, Kim H (2011) Downregulation of erythropoietin receptor by overexpression of phospholipase C-gamma 1 is critical for decrease on focal adhesion in transformed cells. Cell Oncol (Dordr) 34(1):11-21
65. Layon ME, Ackley CJ, West RJ, Lowrey CH (2007) Expression of GATA-1 in a non-hematopoietic cell line induces beta-globin locus control region chromatin structure remodeling and an erythroid pattern of gene expression. J Mol Biol 366(3):737-744
66. Liang K, Esteva FJ, Albarracin C, Stemke-Hale K, Lu Y, Bianchini G, Yang CY, Li Y, Li X, Chen CT, Mills GB, Hortobagyi GN, Mendelsohn J, Hung MC, Fan Z (2010) Recombinant human erythropoietin antagonizes trastuzumab treatment of breast cancer cells via Jak2-mediated Src activation and PTEN inactivation. Cancer Cell 18(5):423-435
67. Kataoka M, Moriya Y, Moriguchi Y, Iwai T, Fujimoto-Ouchi K, Shirane M, Kondoh K, Mori K (2010) Effect of erythropoietin on human tumor growth in xenograft models. Mol Med Report 3(1):95-101
68. LaMontagne KR, Butler J, Marshall DJ, Tullai J, Gechtman Z, Hall C, Meshaw A, Farrell FX (2006) Recombinant epoetins do not stimulate tumor growth in erythropoietin receptor-positive breast carcinoma models. Mol Cancer Ther 5(2):347-355
69. Longmore GD, Pharr PN, Lodish HF (1994) A constitutively activated erythropoietin receptor stimulates proliferation and contributes to transformation of multipotent, committed nonerythroid and erythroid progenitor cells. Mol Cell Biol 14(4):2266-2277
70. McArthur GA, Longmore GD, Klingler K, Johnson GR (1995) Lineage-restricted recruitment of immature hematopoietic progenitor cells in response to Epo after normal hematopoietic cell transfection with EpoR. Exp Hematol 23(7):645-654
71. Pharr PN, Ogawa M, Hofbauer A, Longmore GD (1994) Expression of an activated erythropoietin or a colony-stimulating factor 1 receptor by pluripotent progenitors enhances colony formation but does not induce differentiation. Proc Natl Acad Sci U S A 91(16):7482-7486
72. Gonda TJ, D'Andrea RJ (1997) Activating mutations in cytokine receptors: implications for receptor function and role in disease. Blood 89(2):355-369
73. Le Couedic JP, Mitjavila MT, Villeval JL, Feger F, Gobert S, Mayeux P, Casadevall N, Vainchenker W (1996) Missense mutation of the erythropoietin receptor is a rare event in human erythroid malignancies. Blood 87(4):1502-1511
74. Al-Sheikh M, Mazurier E, Gardie B, Casadevall N, Galacteros F, Goossens M, Wajcman H, Prehu C, Ugo V (2008) A study of 36 unrelated cases with pure erythrocytosis revealed three new mutations in the erythropoietin receptor gene. Haematologica 93(7):1072-1075
75. Rives S, Pahl HL, Florensa L, Bellosillo B, Neusuess A, Estella J, Debatin KM, Kohne E, Schwarz K, Cario H (2007) Molecular genetic analyses in familial and sporadic congenital primary erythrocytosis. Haematologica 92(5):674-677
76. Gordeuk VR, Sergueeva AI, Miasnikova GY, Okhotin D, Voloshin Y, Choyke PL, Butman JA, Jedlickova K, Prchal JT, Polyakova LA (2004) Congenital disorder of oxygen sensing: association of the homozygous Chuvash polycythemia VHL mutation with thrombosis and vascular abnormalities but not tumors. Blood 103(10):3924-3932
77. Chretien S, Moreau-Gachelin F, Apiou F, Courtois G, Mayeux P, Dutrillaux B, Cartron JP, Gisselbrecht S, Lacombe C (1994) Putative oncogenic role of the erythropoietin receptor in murine and human erythroleukemia cells. Blood 83(7):1813-1821
78. Winkelmann JC, Ward J, Mayeux P, Lacombe C, Schimmenti L, Jenkins RB (1995) A translocated erythropoietin receptor gene in a human erythroleukemia cell line (TF-1) expresses an abnormal transcript and a truncated protein. Blood 85(1):179-185
79. Sergeyeva A, Gordeuk VR, Tokarev YN, Sokol L, Prchal JF, Prchal JT (1997) Congenital polycythemia in Chuvashia. Blood 89(6):2148-2154
80. Ang SO, Chen H, Hirota K, Gordeuk VR, Jelinek J, Guan Y, Liu E, Sergueeva AI, Miasnikova GY, Mole D, Maxwell PH, Stockton DW, Semenza GL, Prchal JT (2002) Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia. Nat Genet 32(4):614-621
81. Amsel J, Waterbor JW, Oler J, Rosenwaike I, Marshall K (1982) Relationship of site-specific cancer mortality rates to altitude. Carcinogenesis 3(5):461-465
82. Herbert SP, Stainier DY (2011) Molecular control of endothelial cell behaviour during blood vessel morphogenesis. Nat Rev Mol Cell Biol 12(9):551-564. doi: 10.1038/nrm3176
83. Geudens I, Gerhardt H (2011) Coordinating cell behaviour during blood vessel formation. Development 138(21):4569-4583. doi: 10.1242/dev.062323
84. Ammarguellat F, Gogusev J, Drueke TB (1996) Direct effect of erythropoietin on rat vascular smooth-muscle cell via a putative erythropoietin receptor. Nephrol Dial Transplant 11(4):687-692
85. Fuste B, Diaz-Ricart M, Cases A, Lopez-Pedret J, Ordinas A, Escolar G (2002) Erythropoietin does not modify the prothrombotic effect induced by uremic media on endothelial cells. Haematologica 87(9):1006-1008
86. Lopez Ongil SL, Saura M, Lamas S, Rodriguez PM, Rodriguez PD (1996) Recombinant human erythropoietin does not regulate the expression of endothelin-1 and constitutive nitric oxide synthase in vascular endothelial cells. Exp Nephrol 4(1):37-42
87. Hardee ME, Kirkpatrick JP, Shan S, Snyder SA, Vujaskovic Z, Rabbani ZN, Dewhirst MW, Blackwell KL (2005) Human recombinant erythropoietin (rEpo) has no effect on tumour growth or angiogenesis. Br J Cancer 93(12):1350-1355
88. Pinel S, Barberi-Heyob M, Cohen-Jonathan E, Merlin JL, Delmas C, Plenat F, Chastagner P (2004) Erythropoietin-induced reduction of hypoxia before and during fractionated irradiation contributes to improvement of radioresponse in human glioma xenografts. Int J Radiat Oncol Biol Phys 59(1):250-259
89. Sairah AK, Rasedee A, Sheikh O, Rozita R, Alhaj N (2009) The effects of recombinant human erythropoietin and tamoxifen on growth and angiogenesis of mammary tumor in Sprague-Dawley rat. Am J Pharmacol Toxicol 4(1):12-16
90. Yamaji R, Okada T, Moriya M, Naito M, Tsuruo T, Miyatake K, Nakano Y (1996) Brain capillary endothelial cells express two forms of erythropoietin receptor mRNA. Eur J Biochem 239(2):494-500
91. Crivellato E, Nico B, Vacca A, Djonov V, Presta M, Ribatti D (2004) Recombinant human erythropoietin induces intussusceptive microvascular growth in vivo. Leukemia 18(2):331-336
92. Nico B, Annese T, Guidolin D, Finato N, Crivellato E, Ribatti D (2011) Epo is involved in angiogenesis in human glioma. J Neurooncol 102(1):51-58
93. Ribatti D, Presta M, Vacca A, Ria R, Giuliani R, Dell'Era P, Nico B, Roncali L, Dammacco F (1999) Human erythropoietin induces a pro-angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo. Blood 93(8):2627-2636
94. Steinlein P, Deiner E, Leutz A, Beug H (1994) Recombinant murine erythropoietin receptor expressed in avian erythroid progenitors mediates terminal erythroid differentiation in vitro. Growth Factors 10(1):1-16