Soluble monomeric EphrinA1 is released from tumor cells and is a functional ligand for the EphA2 receptor

Aasheim HC, Munthe E, Funderud S, Smeland EB, Beiske K, Logtenberg T . (2000). A splice variant of human ephrin-A4 encodes a soluble molecule that is secreted by activated human B lymphocytes. Blood 95: 221–230.

Beckmann MP, Cerretti DP, Baum P, Vanden Bos T, James L, Farrah T et al. (1994). Molecular characterization of a family of ligands for eph-related tyrosine kinase receptors. EMBO J 13: 3757–3762.

Brantley-Sieders DM, Fang WB, Hwang Y, Hicks D, Chen J . (2006). Ephrin-A1 facilitates mammary tumor metastasis through an angiogenesis-dependent mechanism mediated by EphA receptor and vascular endothelial growth factor in mice. Cancer Res 66: 10315–10324.

Carles-Kinch K, Kilpatrick KE, Stewart JC, Kinch MS . (2002). Antibody targeting of the EphA2 tyrosine kinase inhibits malignant cell behavior. Cancer Res 62: 2840–2847.

Chakraborti S, Mandal M, Das S, Mandal A, Chakraborti T . (2003). Regulation of matrix metalloproteinases: an overview. Mol Cell Biochem 253: 269–285.

Cheng N, Brantley DM, Liu H, Lin Q, Enriquez M, Gale N et al. (2002). Blockade of EphA receptor tyrosine kinase activation inhibits vascular endothelial cell growth factor-induced angiogenesis. Mol Cancer Res 1: 2–11.

Daniel TO, Stein E, Cerretti DP, St John PL, Robert B, Abrahamson DR . (1996). ELK and LERK-2 in developing kidney and microvascular endothelial assembly. Kidney Int Suppl 57: S73–S81.

Davis S, Gale NW, Aldrich TH, Maisonpierre PC, Lhotak V, Pawson T et al. (1994). Ligands for EPH-related receptor tyrosine kinases that require membrane attachment or clustering for activity. Science 266: 816–819.

Debinski W, Karlsson B, Lindholm L, Siegall CB, Willingham MC, FitzGerald D et al. (1992). Monoclonal antibody C242-Pseudomonas exotoxin A. A specific and potent immunotoxin with antitumor activity on a human colon cancer xenograft in nude mice. J Clin Invest 90: 405–411.

Drescher U, Kremoser C, Handwerker C, Loschinger J, Noda M, Bonhoeffer F . (1995). In vitro guidance of retinal ganglion cell axons by RAGS, a 25 kDa tectal protein related to ligands for Eph receptor tyrosine kinases. Cell 82: 359–370.

Duxbury MS, Ito H, Zinner MJ, Ashley SW, Whang EE . (2004a). EphA2: a determinant of malignant cellular behavior and a potential therapeutic target in pancreatic adenocarcinoma. Oncogene 23: 1448–1456.

Duxbury MS, Ito H, Zinner MJ, Ashley SW, Whang EE . (2004b). Ligation of EphA2 by Ephrin A1-Fc inhibits pancreatic adenocarcinoma cellular invasiveness. Biochem Biophys Res Commun 320: 1096–1102.

Ferguson MA, Williams AF . (1988). Cell-surface anchoring of proteins via glycosyl-phosphatidylinositol structures. Annu Rev Biochem 57: 285–320.

Guo H, Miao H, Gerber L, Singh J, Denning MF, Gilliam AC et al. (2006). Disruption of EphA2 receptor tyrosine kinase leads to increased susceptibility to carcinogenesis in mouse skin. Cancer Res 66: 7050–7058.

Hattori M, Osterfield M, Flanagan JG . (2000). Regulated cleavage of a contact-mediated axon repellent. Science 289: 1360–1365.

Higashiyama S, Nanba D . (2005). ADAM-mediated ectodomain shedding of HB-EGF in receptor cross-talk. Biochim Biophys Acta 1751: 110–117.

Himanen JP, Chumley MJ, Lackmann M, Li C, Barton WA, Jeffrey PD et al. (2004). Repelling class discrimination: ephrin-A5 binds to and activates EphB2 receptor signaling. Nat Neurosci 7: 501–509.

Himanen JP, Rajashankar KR, Lackmann M, Cowan CA, Henkemeyer M, Nikolov DB . (2001). Crystal structure of an Eph receptor-ephrin complex. Nature 414: 933–938.

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.

Holzman LB, Marks RM, Dixit VM . (1990). A novel immediate-early response gene of endothelium is induced by cytokines and encodes a secreted protein. Mol Cell Biol 10: 5830–5838.

Huovila AP, Turner AJ, Pelto-Huikko M, Karkkainen I, Ortiz RM . (2005). Shedding light on ADAM metalloproteinases. Trends Biochem Sci 30: 413–422.

Kinch MS, Carles-Kinch K . (2003). Overexpression and functional alterations of the EphA2 tyrosine kinase in cancer. Clin Exp Metastasis 20: 59–68.

Knoll B, Drescher U . (2002). Ephrin-As as receptors in topographic projections. Trends Neurosci 25: 145–149.

Koolpe M, Dail M, Pasquale EB . (2002). An ephrin mimetic peptide that selectively targets the EphA2 receptor. J Biol Chem 277: 46974–46979.

Kullander K, Klein R . (2002). Mechanisms and functions of Eph and ephrin signalling. Nat Rev Mol Cell Biol 3: 475–486.

Lee DC, Sunnarborg SW, Hinkle CL, Myers TJ, Stevenson MY, Russell WE et al. (2003). TACE/ADAM17 processing of EGFR ligands indicates a role as a physiological convertase. Ann N Y Acad Sci 995: 22–38.

Macrae M, Neve RM, Rodriguez-Viciana P, Haqq C, Yeh J, Chen C et al. (2005). A conditional feedback loop regulates Ras activity through EphA2. Cancer Cell 8: 111–118.

Marquardt T, Shirasaki R, Ghosh S, Andrews SE, Carter N, Hunter T et al. (2005). Coexpressed EphA receptors and ephrin-A ligands mediate opposing actions on growth cone navigation from distinct membrane domains. Cell 121: 127–139.

McBride JL, Ruiz JC . (1998). Ephrin-A1 is expressed at sites of vascular development in the mouse. Mech Dev 77: 201–204.

Meima L, Kljavin IJ, Moran P, Shih A, Winslow JW, Caras IW . (1997). AL-1-induced growth cone collapse of rat cortical neurons is correlated with REK7 expression and rearrangement of the actin cytoskeleton. Eur J Neurosci 9: 177–188.

Miao H, Burnett E, Kinch M, Simon E, Wang B . (2000). Activation of EphA2 kinase suppresses integrin function and causes focal-adhesion-kinase dephosphorylation. Nat Cell Biol 2: 62–69.

Miao H, Wei BR, Peehl DM, Li Q, Alexandrou T, Schelling JR et al. (2001). Activation of EphA receptor tyrosine kinase inhibits the Ras/MAPK pathway. Nat Cell Biol 3: 527–530.

Nakamoto M, Cheng HJ, Friedman GC, McLaughlin T, Hansen MJ, Yoon CH et al. (1996). Topographically specific effects of ELF-1 on retinal axon guidance in vitro and retinal axon mapping in vivo. Cell 86: 755–766.

Noblitt LW, Bangari DS, Shukla S, Knapp DW, Mohammed S, Kinch MS et al. (2004). Decreased tumorigenic potential of EphA2-overexpressing breast cancer cells following treatment with adenoviral vectors that express EphrinA1. Cancer Gene Ther 11: 757–766.

Ogawa K, Pasqualini R, Lindberg RA, Kain R, Freeman AL, Pasquale EB . (2000). The ephrin-A1 ligand and its receptor, EphA2, are expressed during tumor neovascularization. Oncogene 19: 6043–6052.

Pandey A, Shao H, Marks RM, Polverini PJ, Dixit VM . (1995). Role of B61, the ligand for the Eck receptor tyrosine kinase, in TNF-alpha-induced angiogenesis. Science 268: 567–569.

Pasquale EB . (2005). Eph receptor signalling casts a wide net on cell behaviour. Nat Rev Mol Cell Biol 6: 462–475.

Rashid T, Upton AL, Blentic A, Ciossek T, Knoll B, Thompson ID et al. (2005). Opposing gradients of ephrin-As and EphA7 in the superior colliculus are essential for topographic mapping in the mammalian visual system. Neuron 47: 57–69.

Sanderson MP, Dempsey PJ, Dunbar AJ . (2006). Control of ErbB signaling through metalloprotease mediated ectodomain shedding of EGF-like factors. Growth Factors 24: 121–136.

Shao H, Pandey A, O’Shea KS, Seldin M, Dixit VM . (1995). Characterization of B61, the ligand for the Eck receptor protein-tyrosine kinase. J Biol Chem 270: 5636–5641.

Stein E, Lane AA, Cerretti DP, Schoecklmann HO, Schroff AD, Van Etten RL et al. (1998). Eph receptors discriminate specific ligand oligomers to determine alternative signaling complexes, attachment, and assembly responses. Genes Dev 12: 667–678.

Sweeney P, Karashima T, Kim SJ, Kedar D, Mian B, Huang S et al. (2002). Anti-vascular endothelial growth factor receptor 2 antibody reduces tumorigenicity and metastasis in orthotopic prostate cancer xenografts via induction of endothelial cell apoptosis and reduction of endothelial cell matrix metalloproteinase type 9 production. Clin Cancer Res 8: 2714–2724.

Thaker PH, Deavers M, Celestino J, Thornton A, Fletcher MS, Landen CN et al. (2004). EphA2 expression is associated with aggressive features in ovarian carcinoma. Clin Cancer Res 10: 5145–5150.

Toth J, Cutforth T, Gelinas AD, Bethoney KA, Bard J, Harrison CJ . (2001). Crystal structure of an ephrin ectodomain. Dev Cell 1: 83–92.

Turner CP, Pulciani D, Rivkees SA . (2002). Reduction in intracellular calcium levels induces injury in developing neurons. Exp Neurol 178: 21–32.

VanMeter TE, Rooprai HK, Kibble MM, Fillmore HL, Broaddus WC, Pilkington GJ . (2001). The role of matrix metalloproteinase genes in glioma invasion: co-dependent and interactive proteolysis. J Neurooncol 53: 213–235.

Walker-Daniels J, Coffman K, Azimi M, Rhim JS, Bostwick DG, Snyder P et al. (1999). Overexpression of the EphA2 tyrosine kinase in prostate cancer. Prostate 41: 275–280.

Walker-Daniels J, Riese DJ, Kinch MS . (2002). c-Cbl-dependent EphA2 protein degradation is induced by ligand binding. Mol Cancer Res 1: 79–87.

Wang HU, Chen ZF, Anderson DJ . (1998). Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell 93: 741–753.

Wu Q, Suo Z, Risberg B, Karlsson MG, Villman K, Nesland JM . (2004). Expression of Ephb2 and Ephb4 in breast carcinoma. Pathol Oncol Res 10: 26–33.

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.

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.

Xu Q, Wilkinson DG . (1997). Eph-related receptors and their ligands: mediators of contact dependent cell interactions. J Mol Med 75: 576–586.

Zelinski DP, Zantek ND, Stewart JC, Irizarry AR, Kinch MS . (2001). EphA2 overexpression causes tumorigenesis of mammary epithelial cells. Cancer Res 61: 2301–2306.

Zeng G, Hu Z, Kinch MS, Pan CX, Flockhart DA, Kao C et al. (2003). High-level expression of EphA2 receptor tyrosine kinase in prostatic intraepithelial neoplasia. Am J Pathol 163: 2271–2276.

Zhang A, Meng L, Wang Q, Xi L, Chen G, Wang S et al. (2006). Enhanced in vitro invasiveness of ovarian cancer cells through up-regulation of VEGF and induction of MMP-2. Oncol Rep 15: 831–836.

Zucker S, Mirza H, Conner CE, Lorenz AF, Drews MH, Bahou WF et al. (1998). Vascular endothelial growth factor induces tissue factor and matrix metalloproteinase production in endothelial cells: conversion of prothrombin to thrombin results in progelatinase A activation and cell proliferation. Int J Cancer 75: 780–786.