Ephs and ephrins in malignant gliomas

Growth Factors

Volumn 32, Issue 6, 2014, Pages 190-201

  Ferluga, Sara ^a   Debinski, Waldemar ^a  

^a WAKE FOREST SCHOOL OF MEDICINE   (United States)

Author keywords

Brain tumor; Eph; Ephrin; GBM; Glioma

Indexed keywords

EPHRIN A1; EPHRIN A5; EPHRIN B1; EPHRIN B2; EPHRIN DERIVATIVE; EPHRIN RECEPTOR; EPHRIN RECEPTOR A2; EPHRIN RECEPTOR B2; MEMBRANE PROTEIN; UNCLASSIFIED DRUG;

ARTICLE; CELL ADHESION; CELL DIVISION; CELL INVASION; CELL MEMBRANE; CELL MIGRATION; CELL PROLIFERATION; GLIOBLASTOMA; HUMAN; INTERNALIZATION; LIGAND BINDING; PROGNOSIS; PROGRESSION FREE SURVIVAL; PROTEIN FUNCTION; PROTEIN STRUCTURE; SIGNAL TRANSDUCTION;

EID: 84918797006     PISSN: 08977194     EISSN: 10292292     Source Type: Journal    
DOI: 10.3109/08977194.2014.985787     Document Type: Article

References (155)

1. Almog N, Ma L, Raychowdhury R, Schwager C, Erber R, Short S, Hlatky L, et al. 2009. Transcriptional switch of dormant tumors to fast-growing angiogenic phenotype. Cancer Res 69:836-844
2. Altaner C. 2008. Glioblastoma and stem cells. Neoplasma 55:369-374
3. Altieri R, Agnoletti A, Quattrucci F, Garbossa D, Calamo Specchia FM, Bozzaro M, Fornaro R, et al. 2014. Molecular biology of gliomas: Present and future challenges. Transl Med USA 10:29-37
4. Anonymous. 1997. Unified nomenclature for Eph family receptors and their ligands, the ephrins. Eph Nomenclature Committee. Cell 90: 403-404
5. Arvanitis D, Davy A. 2008. Eph/ephrin signaling: Networks. Genes Dev 22:416-429
6. Baglole CJ, Ray DM, Bernstein SH, Feldon SE, Smith TJ, Sime PJ, Phipps RP. 2006. More than structural cells, fibroblasts create and orchestrate the tumor microenvironment. Immunol Invest 35:297-325
7. Bai J,Wang YJ, Liu L, Zhao YL 2014. Ephrin B2 and EphB4 selectively mark arterial and venous vessels in cerebral arteriovenous malformation. J Int Med Res 42:405-415
8. Baumann G, Travieso L, Liebl DJ, Theus MH. 2013. Pronounced hypoxia in the subventricular zone following traumatic brain injury and the neural stem/progenitor cell response. Exp Biol Med (Maywood) 238:830-841
9. Beauchamp A, Debinski W. 2012. Ephs and ephrins in cancer: Ephrin-A1 signalling. Semin Cell Dev Biol 23:109-115
10. Beauchamp A, Lively MO, Mintz A, Gibo D, Wykosky J, Debinski W. 2012. EphrinA1 is released in three forms from cancer cells by matrix metalloproteases. Mol Cell Biol 32:3253-3264
11. Berzofsky JA, Terabe M, Oh S, Belyakov IM, Ahlers JD, Janik JE, Morris JC. 2004. Progress on new vaccine strategies for the immunotherapy and prevention of cancer. J Clin Invest 113:1515-1525
12. Bielamowicz K, Khawja S, Ahmed N. 2013. Adoptive cell therapies for glioblastoma. Front Oncol 3:275
13. Binda E, Visioli A, Giani F, Lamorte G, Copetti M, Pitter KL, Huse JT, et al. 2012. The EphA2 receptor drives self-renewal and tumorigenicity in stem-like tumor-propagating cells from human glioblastomas. Cancer Cell 22:765-780
14. Boyd AW, Bartlett PF, Lackmann M. 2014. Therapeutic targeting of EPH receptors and their ligands. Nat Rev Drug Discov 13:39-62
15. Brantley-Sieders D, Schmidt S, Parker M, Chen J. 2004. Eph receptor tyrosine kinases in tumor and tumor microenvironment. Curr Pharm Des 10:3431-3442
16. Brantley-Sieders DM, Fang WB, Hicks DJ, Zhuang G, Shyr Y, Chen J. 2005. Impaired tumor microenvironment in EphA2-deficient mice inhibits tumor angiogenesis and metastatic progression. FASEB J 19: 1884-1886
17. Broniscer A, Baker SD, Wetmore C, Pai Panandiker AS, Huang J, Davidoff AM, Onar-Thomas A, et al. 2013. Phase I trial, pharmacokinetics, and pharmacodynamics of vandetanib and dasatinib in children with newly diagnosed diffuse intrinsic pontine glioma. Clin Cancer Res 19:3050-3058
18. Bruce V, Olivieri G, Eickelberg O, Miescher GC. 1999. Functional activation of EphA5 receptor does not promote cell proliferation in the aberrant EphA5 expressing human glioblastoma U-118 MG cell line. Brain Res 821:169-176
19. Carmeliet P. 2003. Angiogenesis in health and disease. Nat Med 9: 653-660
20. Carruthers R, Ahmed SU, Strathdee K, Gomez-Roman N, Amoah-Buahin E, Watts C, Chalmers AJ. 2014. Abrogation of radioresistance in glioblastoma stem-like cells by inhibition of ATM kinase. Mol Oncol [Epub ahead of print]. doi: 10.1016/j.molonc.2014.08.003
21. Cavodeassi F, Ivanovitch K, Wilson SW. 2013. Eph/Ephrin signalling maintains eye field segregation from adjacent neural plate territories during forebrain morphogenesis. Development 140:4193-4202
22. Chang Q, Jorgensen C, Pawson T, Hedley DW. 2008. Effects of dasatinib on EphA2 receptor tyrosine kinase activity and downstream signalling in pancreatic cancer. Br J Cancer 99:1074-1082
23. Charles NA, Holland EC, Gilbertson R, Glass R, Kettenmann H. 2012. The brain tumor microenvironment. Glia 60:502-514
24. Chatzizacharias NA, Giaginis CT, Agapitos E, Theocharis SE. 2014. The role of ephrins' receptors and ephrins' ligands in normal placental development and disease. Expert Opin Ther Targets 18:269-275
25. Chen J, Song W, Amato K. 2014. Eph receptor tyrosine kinases in cancer stem cells. Cytokine Growth Factor Rev [Epub ahead of print]. doi: 10.1016/j.cytogfr.2014.05.001
26. Chen R, Nishimura MC, Bumbaca SM, Kharbanda S, Forrest WF, Kasman IM, Greve JM, et al. 2010. A hierarchy of self-renewing tumor-initiating cell types in glioblastoma. Cancer Cell 17:362-375
27. Cheng N, Brantley DM, Chen J. 2002a. The ephrins and Eph receptors in angiogenesis. Cytokine Growth Factor Rev 13:75-85
28. Cheng N, Brantley DM, Liu H, Lin Q, Enriquez M, Gale N, Yancopoulos G, et al. 2002b. Blockade of EphA receptor tyrosine kinase activation inhibits vascular endothelial cell growth factorinduced angiogenesis. Mol Cancer Res 1:2-11
29. Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, et al. 2014. Bevacizumab Plus Radiotherapy-Temozolomide for Newly Diagnosed Glioblastoma. N Engl J Med 370:709-722
30. Chow KK, Naik S, Kakarla S, Brawley VS, Shaffer DR, Yi Z, Rainusso N, et al. 2013. T cells redirected to EphA2 for the immunotherapy of glioblastoma. Mol Ther 21:629-637
31. Clavreul A, Guette C, Faguer R, Tetaud C, Boissard A, Lemaire L, Rousseau A, et al. 2014. Glioblastoma-Associated Stromal Cells (GASCs) from Histologically Normal Surgical Margins Have A Myofibroblast Phenotype and Angiogenic Properties. J Pathol 233: 74-88
32. Clifford MA, Athar W, Leonard CE, Russo A, Sampognaro PJ, Van Der Goes MS, Burton DA, et al. 2014. EphA7 signaling guides cortical dendritic development and spine maturation. Proc Natl Acad Sci USA 111:4994-4999
33. Conover JC, Doetsch F, Garcia-Verdugo JM, Gale NW, Yancopoulos GD, Alvarez-Buylla A. 2000. Disruption of Eph/ephrin signaling affects migration and proliferation in the adult subventricular zone. Nat Neurosci 3:1091-1097
34. Coulthard MG, Duffy S, Down M, Evans B, Power M, Smith F, Stylianou C, et al. 2002. The role of the Eph-ephrin signalling system in the regulation of developmental patterning. Int J Dev Biol 46: 375-384
35. Coulthard MG, Morgan M, Woodruff TM, Arumugam TV, Taylor SM, Carpenter TC, Lackmann M, Boyd AW. 2012. Eph/Ephrin Signaling in Injury and Inflammation. Am J Pathol 181:1493-1503
36. Cramer KS, Gabriele ML. 2014. Axon guidance in the auditory system: Multiple functions of Eph receptors. Neuroscience 277C:152-162
37. Daar IO. 2012. Non-SH2/PDZ reverse signaling by ephrins. Semin Cell Dev Biol 23:65-74
38. Daniel P, Filiz G, Brown DV, Hollande F, Gonzales M, D'Abaco G, Papalexis N, et al. 2014. Selective CREB-dependent cyclin expression mediated by the PI3K and MAPK pathways supports glioma cell proliferation. Oncogenesis 3:e108
39. Day BW, Stringer BW, Al-Ejeh F, Ting MJ, Wilson J, Ensbey KS, Jamieson PR, et al. 2013. EphA3 maintains tumorigenicity and is a therapeutic target in glioblastoma multiforme. Cancer Cell 23: 238-248
40. Day BW, Stringer BW, Boyd AW. 2014. Eph Receptors As Therapeutic Targets in Glioblastoma. Br J Cancer 111:1255-1261
41. Debinski W. 2002. Local treatment of brain tumors with targeted chimera cytotoxic proteins. Cancer Invest 20:801-809
42. Debinski W, Gibo DM, Hulet SW, Connor JR, Gillespie GY. 1999. Receptor for interleukin 13 is a marker and therapeutic target for human high-grade gliomas. Clin Cancer Res 5:985-990
43. Debinski W, Tatter SB. 2009. Convection-enhanced delivery for the treatment of brain tumors. Expert Rev Neurother 9:1519-1527
44. Dohn M, Jiang J, Chen X. 2001. Receptor tyrosine kinase EphA2 is regulated by p53-family proteins and induces apoptosis. Oncogene 20: 6503-6515
45. Duxbury MS, Ito H, Zinner MJ, Ashley SW, Whang EE. 2004. EphA2: A determinant of malignant cellular behavior and a potential therapeutic target in pancreatic adenocarcinoma. Oncogene 23:1448-1456
46. Egeblad M, Nakasone ES, Werb Z. 2010. Tumors as organs: Complex tissues that interface with the entire organism. Dev Cell 18:884-901
47. Elowe S, Holland SJ, Kulkarni S, Pawson T. 2001. Downregulation of the Ras-mitogen-Activated protein kinase pathway by the EphB2 receptor tyrosine kinase is required for ephrin-induced neurite retraction. Mol Cell Biol 21:7429-7441
48. Ende G, Poitz DM, Strasser RH, Jellinghaus S. 2014. The role of the Eph/ephrin-system in atherosclerotic plaque development: A complex puzzle. Cardiovasc Pathol 23:251
49. Ethell IM, Ethell DW. 2007. Matrix metalloproteinases in brain Development and remodeling: Synaptic functions and targets. J Neurosci Res 85:2813-2823
50. Ferluga S, Hantgan R, Goldgur Y, Himanen JP, Nikolov DB, DebinskiW. 2013. Biological and structural characterization of glycosylation on ephrin-A1, a preferred ligand for EphA2 receptor tyrosine kinase. J Biol Chem 288:18448-18457
51. Frugier T, Conquest A, McLean C, Currie P, Moses D, Goldshmit Y. 2012. Expression and Activation of EphA4 in the Human Brain after Traumatic Injury. J Neuropathol Exp Neurol 71:242-250
52. Fukai J, Yokote H, Yamanaka R, Arao T, Nishio K, Itakura T. 2008. EphA4 promotes cell proliferation and migration through a novel EphA4-FGFR1 signaling pathway in the human glioma U251 cell line. Mol Cancer Ther 7:2768-2778
53. Germano IM, Binello E 2014. Stem cells and gliomas: Past, present, and future. J Neurooncol 119:547-555
54. Giaginis C, Tsoukalas N, Bournakis E, Alexandrou P, Kavantzas N, Patsouris E, Theocharis S. 2014. Ephrin (Eph) receptor A1, A4, A5 and A7 expression in human non-small cell lung carcinoma: Associations with clinicopathological parameters, tumor proliferative capacity and patients' survival. BMC Clin Pathol 14:8
55. Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, et al 2014. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 370: 699-708
56. Glass R, Synowitz M. 2014. CNS macrophages and peripheral myeloid cells in brain tumours. Acta Neuropathol 128:347-362
57. Golik AN. 1991. Characteristics of premorbid (pre-manifest) personality traits in schizophrenia in children and adolescents with psychopathic disorders. Zh Nevropatol Psikhiatr Im S S Korsakova 91:90-93
58. Gont A, Hanson JE, Lavictoire SJ, Parolin DA, Daneshmand M, Restall IJ, Soucie M, et al. 2013. PTEN loss represses glioblastoma tumor initiating cell differentiation via inactivation of Lgl1. Oncotarget 4:1266-1279
59. Greene AC, Lord SJ, Tian A, Rhodes C, Kai H, Groves JT. 2014. Spatial organization of EphA2 at the cell-cell interface modulates transendocytosis of ephrinA1. Biophys J 106:2196-2205
60. Hamed HA, Tavallai S, Grant S, Poklepovic A, Dent P. 2014. Sorafenib/ Regorafenib and Lapatinib interact to kill CNS tumor cells. J Cell Physiol [Epub ahead of print]. doi: 10.1002/jcp.24689
61. Han X, Zhang W, Yang X, Wheeler CG, Langford CP, Wu L, Filippova N, et al 2014. The role of Src family kinases in growth and migration of glioma stem cells. Int J Oncol 45:302-310
62. Hanahan D, Weinberg RA. 2011. Hallmarks of cancer: The next generation. Cell 144:646-674
63. Hanahan D, Weinberg RA. 2000. The hallmarks of cancer. Cell 100: 57-70
64. Hatano M, Eguchi J, Tatsumi T, Kuwashima N, Dusak JE, Kinch MS, Pollack IF, et al. 2005. EphA2 as a glioma-Associated antigen: A novel target for glioma vaccines. Neoplasia 7:717-722
65. Hatano M, Kuwashima N, Tatsumi T, Dusak JE, Nishimura F, Reilly KM, Storkus WJ, Okada H. 2004. Vaccination with EphA2-derived T cellepitopes promotes immunity against both EphA2-expressing and EphA2-negative tumors. J Transl Med 2:40
66. Himanen JP, Chumley MJ, Lackmann M, Li C, Barton WA, Jeffrey PD, Vearing C, et al. 2004. Repelling class discrimination: Ephrin-A5 binds to and activates EphB2 receptor signaling. Nat Neurosci 7: 501-509
67. Hoelzinger DB, Demuth T, Berens ME. 2007. Autocrine factors that sustain glioma invasion and paracrine biology in the brain microenvironment. J Natl Cancer Inst 99:1583-1593
68. Hong B, van Den Heuvel AP, Prabhu VV, Zhang S, El-Deiry WS. 2014. Targeting tumor suppressor p53 for cancer therapy: Strategies, challenges and opportunities. Curr Drug Targets 15:80-89
69. Huang F, Reeves K, Han X, Fairchild C, Platero S, Wong TW, Lee F, et al. 2007. Identification of candidate molecular markers predicting sensitivity in solid tumors to dasatinib: Rationale for patient selection. Cancer Res 67:2226-2238
70. Ieguchi K, Tomita T, Omori T, Komatsu A, Deguchi A, Masuda J, Duffy SL, et al. 2014. ADAM12-cleaved ephrin-A1 contributes to lung metastasis. Oncogene 33:2179-2190
71. Janes PW, Nievergall E, Lackmann M. 2012. Concepts and consequences of Eph receptor clustering. Semin Cell Dev Biol 23:43-50
72. Janes PW, Saha N, Barton WA, Kolev MV, Wimmer-Kleikamp SH, Nievergall E, Blobel CP, et al. 2005. Adam meets Eph: An ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell 123:291-304
73. Jeon HM, Kim SH, Jin X, Park JB, Joshi K, Nakano I, Kim H. 2014. Crosstalk between glioma-initiating cells and endothelial cells drives tumor progression. Cancer Res 74:4482-4492
74. Jellinghaus S, Poitz DM, Ende G, Augstein A, Weinert S, Stutz B, Braun-Dullaeus RC, et al. 2013. Ephrin-A1/EphA4-mediated adhesion of monocytes to endothelial cells. Biochim Biophys Acta 1833: 2201-2211
75. Jin M, Komohara Y, Shichijo S, Yamanaka R, Nikawa J, Itoh K, Yamada A. 2008. Erythropoietin-producing hepatocyte B6 variantderived peptides with the ability to induce glioma-reactive cytotoxic T lymphocytes in human leukocyte antigen-A2+ glioma patients. Cancer Sci 99:1656-1662
76. Joy AM, Beaudry CE, Tran NL, Ponce FA, Holz DR, Demuth T, Berens ME. 2003. Migrating glioma cells activate the PI3-K pathway and display decreased susceptibility to apoptosis. J Cell Sci 116: 4409-4417
77. Julich D, Mould AP, Koper E, Holley SA. 2009. Control of extracellular matrix assembly along tissue boundaries via Integrin and Eph/Ephrin signaling. Development 136:2913-2921
78. Klein R, Kania A. 2014. Ephrin signalling in the developing nervous system. Curr Opin Neurobiol 27:16-24
79. Laske DW, Youle RJ, Oldfield EH. 1997. Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors. Nat Med 3:1362-1368
80. Leung K. 2013. Cy5.5-Anti-ephrin receptor B4 (EphB4) humanized monoclonal antibody hAb47. Molecular Imaging and Contrast Agent Database (MICAD) [Online]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013. Available from: http:// www.ncbi.nlm.nih.gov/books/NBK137711/ [Accessed 09 May 2013
81. Li JJ, Liu DP, Liu GT, Xie D. 2009. EphrinA5 acts as a tumor suppressor in glioma by negative regulation of epidermal growth factor receptor. Oncogene 28:1759-1768
82. Li W, Graeber MB. 2012. The molecular profile of microglia under the influence of glioma. Neuro Oncol 14:958-978
83. Li X, Wang Y, Zhen H, Yang H, Fei Z, Zhang J, Liu W, Zhang X. 2007. Expression of EphA2 in human astrocytic tumors: Correlation with pathologic grade, proliferation and apoptosis. Tumour Biol 28: 165-172
84. Lisabeth EM, Falivelli G, Pasquale EB. 2013. Eph receptor signaling and ephrins. Cold Spring Harb Perspect Biol 5:1-28
85. Lisle JE, Mertens-Walker I, Rutkowski R, Herington AC, Stephenson SA. 2013. Eph receptors and their ligands: Promising molecular biomarkers and therapeutic targets in prostate cancer. Biochim Biophys Acta 1835: 243-257
86. Liu F, Park PJ, Lai W, Maher E, Chakravarti A, Durso L, Jiang X, et al. 2006. A genome-wide screen reveals functional gene clusters in the cancer genome and identifies EphA2 as a mitogen in glioblastoma. Cancer Res 66:10815-10823
87. Lombardo LJ, Lee FY, Chen P, Norris D, Barrish JC, Behnia K, Castaneda S, et al. 2004. Discovery of N-(2-chloro-6-methyl-phenyl)-2-(6-(4-(2-hydroxyethyl)-piperazin-1-yl)-2-methylpyrimidin-4-ylamino) thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. J Med Chem 47:6658-6661
88. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P. 2007. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114: 97-109
89. Macrae M, Neve RM, Rodriguez-Viciana P, Haqq C, Yeh J, Chen C, Gray JW, McCormick F. 2005. A conditional feedback loop regulates Ras activity through EphA2. Cancer Cell 8:111-118
90. Mancia F, Shapiro L. 2005. ADAM and Eph: How Ephrin-signaling cells become detached. Cell 123:185-187
91. Mantovani A, Sica A. 2010. Macrophages, innate immunity and cancer: Balance, tolerance, and diversity. Curr Opin Immunol 22:231-237
92. McNamara MG, Sahebjam S, Mason WP. 2013. Emerging biomarkers in glioblastoma. Cancers (Basel) 5:1103-1119
93. Meyer S, Hafner C, Guba M, Flegel S, Geissler EK, Becker B, Koehl GE, et al. 2005. Ephrin-B2 overexpression enhances integrinmediated ECM-Attachment and migration of B16 melanoma cells. Int J Oncol 27:1197-1206
94. Miao H, Gale NW, Guo H, Qian J, Petty A, Kaspar J, Murphy AJ, et al. 2014. EphA2 promotes infiltrative invasion of glioma stem cells in vivo through cross-Talk with Akt and regulates stem cell properties. Oncogene [Epub ahead of print]. doi: 10.1038/onc.2013.590
95. Miao H, Li DQ, Mukherjee A, Guo H, Petty A, Cutter J, Basilion JP, et al. 2009. EphA2 mediates ligand-dependent inhibition and ligandindependent promotion of cell migration and invasion via a reciprocal regulatory loop with Akt. Cancer Cell 16:9-20
96. Mintz A, Gibo DM, Madhankumar AB, Debinski W. 2003. Molecular targeting with recombinant cytotoxins of interleukin-13 receptor alpha2-expressing glioma. J Neurooncol 64:117-123
97. Nagane M. 2014. Anti-Angiogenic therapy for malignant glioma. Gan To Kagaku Ryoho 41:141-147
98. Nakada M, Anderson EM, Demuth T, Nakada S, Reavie LB, Drake KL, Hoelzinger DB, Berens ME. 2010. the Phosphorylation of ephrin-B2 Ligand Promotes Glioma Cell Migration and Invasion. Int J Cancer 126: 1155-1165
99. Nakada M, Hayashi Y, Hamada J. 2011. Role of Eph/ephrin tyrosine kinase in malignant glioma. Neuro Oncol 13:1163-1170
100. Nakada M, Kita D, Teng L, Pyko IV, Watanabe T, Hayashi Y, Hamada J. 2013. Receptor tyrosine kinases: Principles and functions in glioma invasion. Adv Exp Med Biol 986:143-170
101. Nakada M, Niska JA, Miyamori H, McDonough WS, Wu J, Sato H, Berens ME. 2004. The phosphorylation of EphB2 receptor regulates migration and invasion of human glioma cells. Cancer Res 64: 3179-3185
102. Noren NK, Lu M, Freeman AL, Koolpe M, Pasquale EB. 2004. Interplay between EphB4 on tumor cells and vascular ephrin-B2 regulates tumor growth. Proc Natl Acad Sci USA 101:5583-5588
103. Novellino L, Castelli C, Parmiani G. 2005. A listing of human tumor antigens recognized by T cells: March 2004 update. Cancer Immunol Immunother 54:187-207
104. Oike Y, Ito Y, Hamada K, Zhang XQ, Miyata K, Arai F, Inada T, et al. 2002. Regulation of vasculogenesis and angiogenesis by EphB/ephrin-B2 signaling between endothelial cells and surrounding mesenchymal cells. Blood 100:1326-1333
105. Okada H, Kalinski P, Ueda R, Hoji A, Kohanbash G, Donegan TE, Mintz AH, et al. 2011. Induction of CD8+ T-cell Responses Against Novel Glioma-Associated Antigen Peptides and Clinical Activity by Vaccinations with {Alpha}-Type 1 Polarized Dendritic Cells and Polyinosinic-polycytidylic Acid Stabilized by Lysine and Carboxymethylcellulose in Patients with Recurrent Malignant Glioma. J Clin Oncol 29:330-336
106. Paavilainen S, Grandy D, Karelehto E, Chang E, Susi P, Erdjument-Bromage H, Nikolov D, Himanen J. 2013. High-level expression of a full-length Eph receptor. Protein Expr Purif 92:112-118
107. Palmer A, Klein R. 2003. Multiple roles of ephrins in morphogenesis, neuronal networking, and brain function. Genes Dev 17:1429-1450
108. Pandey A, Lazar DF, Saltiel AR, Dixit VM. 1994. Activation of the Eck receptor protein tyrosine kinase stimulates phosphatidylinositol 3-kinase activity. J Biol Chem 269:30154-30157
109. Parri M, Buricchi F, Giannoni E, Grimaldi G, Mello T, Raugei G, Ramponi G, Chiarugi P. 2007. EphrinA1 activates a Src/focal adhesion kinase-mediated motility response leading to rho-dependent actino/myosin contractility. J Biol Chem 282:19619-19628
110. Parmaksiz G, Czabanka M, Vinci M, Vajkoczy P. 2014. Antiangiogenic Therapy Inhibits the Recruitment of Vascular Accessory Cells to the Perivascular Niche in Glioma Angiogenesis. J Vasc Res 51:102-109
111. Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, et al. 2008. An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807-1812
112. Pasquale EB. 2005. Eph receptor signalling casts a wide net on cell behaviour. Nat Rev Mol Cell Biol 6:462-475
113. Pellegatta S, Cuppini L, Finocchiaro G. 2011. Brain cancer immunoediting: Novel examples provided by immunotherapy of malignant gliomas. Expert Rev Anticancer Ther 11:1759-1774
114. Petty A, Myshkin E, Qin H, Guo H, Miao H, Tochtrop GP, Hsieh JT, et al. 2012. A small molecule agonist of EphA2 receptor tyrosine kinase inhibits tumor cell migration in vitro and prostate cancer metastasis in vivo. PLoS One 7:e42120
115. Pratt RL, Kinch MS. 2002. Activation of the EphA2 tyrosine kinase stimulates the MAP/ERK kinase signaling cascade. Oncogene 21: 7690-7699
116. Reardon DA, Freeman G, Wu C, Chiocca EA, Wucherpfennig KW, Wen PY, Fritsch EF, et al. 2014. Immunotherapy advances for glioblastoma. Neuro Oncol 16:1441-1458
117. Rix U, Hantschel O, Durnberger G, Remsing Rix LL, Planyavsky M, Fernbach NV, Kaupe I, et al. 2007. Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib, and dasatinib reveal novel kinase and nonkinase targets. Blood 110:4055-4063
118. Ruella M, Kalos M. 2014. Adoptive immunotherapy for cancer. Immunol Rev 257:14-38
119. Salaita K, Nair PM, Petit RS, Neve RM, Das D, Gray JW, Groves JT. 2010. Restriction of receptor movement alters cellular response: Physical force sensing by EphA2. Science 327:1380-1385
120. Sawamiphak S, Seidel S, Essmann CL, Wilkinson GA, Pitulescu ME, AckerT, Acker-Palmer A. 2010. Ephrin-B2 regulatesVEGFR2function in Developmental and tumour angiogenesis. Nature 465:487-491
121. Schreiber RD, Old LJ, Smyth MJ. 2011. Cancer immunoediting: Integrating immunity's roles in cancer suppression and promotion. Science 331:1565-1570
122. Sikkema AH, den Dunnen WF, Hulleman E, van Vuurden DG, Garcia-Manero G, Yang H, Scherpen FJ, et al. 2012. EphB2 activity plays a pivotal role in pediatric medulloblastoma cell adhesion and invasion. Neuro Oncol 14:1125-1135
123. Stupp R, Hegi ME, Gorlia T, Perry JR, Erridge S, Reardon DA, Markivskyy A, et al. 2013. Standard chemoradiotherapy 'cilengitide in newly diagnosed glioblastoma (GBM): Updated results and subgroup analyses of the international randomized phase III CENTRIC trial (EORTC trial #26071-22072/Canadian Brain Tumor Consortium). Program and abstracts of the European Cancer Congress 2013; Amsterdam, The Netherlands. Abstract 3302
124. Stupp R, Mason WP, van Den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, et al. 2005. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352: 987-996
125. Takahashi Y, Itoh M, Nara N, Tohda S. 2014. Effect of EPH-ephrin signaling on the growth of human leukemia cells. Anticancer Res 34: 2913-2918
126. Teng L, Nakada M, Furuyama N, Sabit H, Furuta T, Hayashi Y, Takino T, et al. 2013. Ligand-dependent EphB1 signaling suppresses glioma invasion and correlates with patient survival. Neuro Oncol 15: 1710-1720
127. Thaker PH, Deavers M, Celestino J, Thornton A, Fletcher MS, Landen CN, Kinch MS, et al. 2004. EphA2 expression is associated with aggressive features in ovarian carcinoma. Clin Cancer Res 10: 5145-5150
128. Tong J, Elowe S, Nash P, Pawson T. 2003. Manipulation of EphB2 regulatory motifs and SH2 binding sites switches MAPK signaling and biological activity. J Biol Chem 278:6111-6119
129. Tu Y, He S, Fu J, Li G, Xu R, Lu H, Deng J. 2012. Expression of EphrinB2 and EphB4 in glioma tissues correlated to the progression of glioma and the prognosis of glioblastoma patients. Clin Transl Oncol 14:214-220
130. Vail ME, Murone C, Tan A, Hii L, Abebe D, Janes PW, Lee FT, et al. 2014. Targeting EphA3 inhibits cancer growth by disrupting the tumor stromal microenvironment. Cancer Res 74:4470-4481
131. Vindis C, Cerretti DP, Daniel TO, Huynh-Do U. 2003. EphB1 recruits c-Src and p52Shc to activate MAPK/ERK and promote chemotaxis. J Cell Biol 162:661-671
132. Vogelbaum MA, Iannotti CA. 2012. Convection-enhanced delivery of therapeutic agents into the brain. Handb Clin Neurol 104: 355-362
133. Wainwright DA, Dey M, Chang A, Lesniak MS. 2013. Targeting Tregs in malignant brain cancer: Overcoming IDO. Front Immunol 4:116
134. Wainwright DA, Nigam P, Thaci B, Dey B, Lesniak MS. 2012. Recent developments on immunotherapy for brain cancer. Expert Opin Emerg Drugs 17:181-202
135. Walker-Daniels J, Riese II DJ, Kinch MS. 2002. c-Cbl-dependent EphA2 protein Degradation is induced by ligand binding. Mol Cancer Res 1: 79-87
136. Wang LF, Fokas E, Bieker M, Rose F, Rexin P, Zhu Y, Pagenstecher A, et al. 2008a. Increased expression of EphA2 correlates with adverse outcome in primary and recurrent glioblastoma multiforme patients. Oncol Rep 19:151-156
137. Wang LF, Fokas E, Juricko J, You A, Rose F, Pagenstecher A, Engenhart-Cabillic R, An HX. 2008b. Increased expression of EphA7 correlates with adverse outcome in primary and recurrent glioblastoma multiforme patients. BMC Cancer 8:79
138. Wang SD, Rath P, Lal B, Richard JP, Li Y, Goodwin CR, Laterra J, Xia S. 2012. EphB2 receptor controls proliferation/migration Dichotomy of glioblastoma by interacting with focal adhesion kinase. Oncogene 31:5132-5143
139. Wick W, Weller M, Weiler M, Batchelor T, Yung AW, Platten M. 2011. Pathway inhibition: Emerging molecular targets for treating glioblastoma. Neuro Oncol 13:566-579
140. Wilhelm SM, Dumas J, Adnane L, Lynch M, Carter CA, Schutz G, Thierauch KH, Zopf D. 2011. Regorafenib (BAY 73-4506): A New Oral Multikinase Inhibitor of Angiogenic, Stromal and Oncogenic Receptor Tyrosine Kinases with Potent Preclinical Antitumor Activity. Int J Cancer 129:245-255
141. Wilson TA, Karajannis MA, Harter DH. 2014. Glioblastoma multiforme: State of the art and future therapeutics. Surg Neurol Int 5:64
142. Wykosky J, Debinski W. 2008. The EphA2 receptor and ephrinA1 ligand in solid tumors: Function and therapeutic targeting. Mol Cancer Res 6: 1795-1806
143. Wykosky J, Gibo DM, Debinski W. 2007. A novel, potent, and specific ephrinA1-based cytotoxin against EphA2 receptor expressing tumor cells. Mol Cancer Ther 6:3208-3218
144. Wykosky J, Gibo DM, Stanton C, Debinski W. 2005. EphA2 as a novel molecular marker and target in glioblastoma multiforme. Mol Cancer Res 3:541-551
145. Wykosky J, Gibo DM, Stanton C, Debinski W. 2008a. Interleukin-13 receptor alpha 2, EphA2, and Fos-related antigen 1 as molecular denominators of high-grade astrocytomas and specific targets for combinatorial therapy. Clin Cancer Res 14:199-208
146. Wykosky J, Palma E, Gibo DM, Ringler S, Turner CP, Debinski W. 2008b. Soluble monomeric EphrinA1 is released from tumor cells and is a functional ligand for the EphA2 receptor. Oncogene 27: 7260-7273
147. Yamaguchi Y, Pasquale EB. 2004. Eph receptors in the adult brain. Curr Opin Neurobiol 14:288-296
148. Yang NY, Fernandez C, Richter M, Xiao Z, Valencia F, Tice DA, Pasquale EB. 2011. Crosstalk of the EphA2 receptor with a serine/ threonine phosphatase suppresses the Akt-mTORC1 pathway in cancer cells. Cell Signal 23:201-212
149. Yin H, Lu C, Tang Y, Wang H, Wang J. 2013. Enhanced expression of EphrinB1 is associated with lymph node metastasis and poor prognosis in breast cancer. Cancer Biomark 13:261-267
150. Yu G, Luo H, Wu Y, Wu J. 2003. Ephrin B2 induces T cell costimulation. J Immunol 171:106-114
151. Yu J, Zhang L, Hwang PM, Rago C, Kinzler KW, Vogelstein B. 1999. Identification and classification of p53-regulated genes. Proc Natl Acad Sci USA 96:14517-14522
152. Yun J, Rothrock RJ, Canoll P, Bruce JN 2013. Convection-enhanced delivery for targeted delivery of antiglioma agents: The translational experience. J Drug Deliv 2013:107573
153. Zelinski DP, Zantek ND, Stewart JC, Irizarry AR, Kinch MS. 2001. EphA2 overexpression causes tumorigenesis of mammary epithelial cells. Cancer Res 61:2301-2306
154. Zhao X, Guan JL. 2011. Focal adhesion kinase and its signaling pathways in cell migration and angiogenesis. Adv Drug Deliv Rev 63: 610-615
155. Ziyad S, Iruela-Arispe ML. 2011. Molecular mechanisms of tumor angiogenesis. Genes Cancer 2:1085-1096