Epidermal Growth Factor, Latrophilin, and Seven Transmembrane Domain-containing Protein 1 Marker, a Novel Angiogenesis Marker

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2016 Jan 1

PMID 26719704

Citations 17

Authors

Florentina Serban

Stefan-Alexandru Artene

Ada Maria Georgescu

Stefana Oana Purcaru

Daniela Elise Tache

Oana Alexandru

Anica Dricu

Affiliations

Soon will be listed here.

Abstract

Epidermal growth factor, latrophilin, and seven transmembrane domain-containing protein 1 on chromosome 1 (ELTD1), an orphan adhesion G-protein coupled receptor, was reported as a regulator of angiogenesis, also involved in cancer progression and development. More recently, ELTD1 was identified as a potential new tumor marker for high-grade glioma. ELTD1, belongs to the G-protein coupled receptor superfamily that comprises the biggest receptor family in the human genome. Following the discovery of ELTD1 almost a decade ago, only a few research groups have attempted to find its role in normal and tumor cells, important information about this receptor remaining still unknown. The ELTD1 ligand has not currently been identified and intracellular signaling studies have not yet been performed in normal or tumor cells. Although the current published data on ELTD1 function and structure are rather limited, this receptor seems to be very important, not only as biomarker, but also as molecular target in glioblastoma. This review summarizes and discusses the current knowledge on ELTD1 structure, function, and its role in both physiological and tumoral angiogenesis.

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References

Harkensee C, Oka A, Onizuka M, Middleton P, Inoko H, Nakaoka H . Microsatellite scanning of the immunogenome associates MAPK14 and ELTD1 with graft-versus-host disease in hematopoietic stem cell transplantation. Immunogenetics. 2013; 65(6):417-27. DOI: 10.1007/s00251-013-0691-z. View

Stupp R, Hegi M, Mason W, van den Bent M, Taphoorn M, Janzer R . Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009; 10(5):459-66. DOI: 10.1016/S1470-2045(09)70025-7. View

Krex D, Klink B, Hartmann C, von Deimling A, Pietsch T, Simon M . Long-term survival with glioblastoma multiforme. Brain. 2007; 130(Pt 10):2596-606. DOI: 10.1093/brain/awm204. View

Fredriksson R, Lagerstrom M, Lundin L, Schioth H . The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol Pharmacol. 2003; 63(6):1256-72. DOI: 10.1124/mol.63.6.1256. View

Nechiporuk T, Urness L, Keating M . ETL, a novel seven-transmembrane receptor that is developmentally regulated in the heart. ETL is a member of the secretin family and belongs to the epidermal growth factor-seven-transmembrane subfamily. J Biol Chem. 2000; 276(6):4150-7. DOI: 10.1074/jbc.M004814200. View

Alessi P, Leali D, Camozzi M, Cantelmo A, Albini A, Presta M . Anti-FGF2 approaches as a strategy to compensate resistance to anti-VEGF therapy: long-pentraxin 3 as a novel antiangiogenic FGF2-antagonist. Eur Cytokine Netw. 2010; 20(4):225-34. DOI: 10.1684/ecn.2009.0175. View

Anderson K, Pan L, Yang X, Hughes V, Walls J, Dominguez M . Angiogenic sprouting into neural tissue requires Gpr124, an orphan G protein-coupled receptor. Proc Natl Acad Sci U S A. 2011; 108(7):2807-12. PMC: 3041062. DOI: 10.1073/pnas.1019761108. View

Cohen A, Colman H . Glioma biology and molecular markers. Cancer Treat Res. 2014; 163:15-30. DOI: 10.1007/978-3-319-12048-5_2. View

Cullen M, Elzarrad M, Seaman S, Zudaire E, Stevens J, Yang M . GPR124, an orphan G protein-coupled receptor, is required for CNS-specific vascularization and establishment of the blood-brain barrier. Proc Natl Acad Sci U S A. 2011; 108(14):5759-64. PMC: 3078373. DOI: 10.1073/pnas.1017192108. View

10.

Haaland B, Chopra A, Acharyya S, Fay A, de Lima Lopes G . Comparative effectiveness of approved first-line anti-angiogenic and molecularly targeted therapeutic agents in the treatment of good and intermediate risk metastatic clear cell renal cell carcinoma. BMC Cancer. 2014; 14:592. PMC: 4148555. DOI: 10.1186/1471-2407-14-592. View

11.

Formstone C . 7TM-Cadherins: developmental roles and future challenges. Adv Exp Med Biol. 2011; 706:14-36. DOI: 10.1007/978-1-4419-7913-1_2. View

12.

Favara D, Banham A, Harris A . A review of ELTD1, a pro-angiogenic adhesion GPCR. Biochem Soc Trans. 2014; 42(6):1658-64. DOI: 10.1042/BST20140216. View

13.

Pickering C, Hagglund M, Szmydynger-Chodobska J, Marques F, Palha J, Waller L . The Adhesion GPCR GPR125 is specifically expressed in the choroid plexus and is upregulated following brain injury. BMC Neurosci. 2008; 9:97. PMC: 2571103. DOI: 10.1186/1471-2202-9-97. View

14.

van Beijnum J, Nowak-Sliwinska P, Huijbers E, Thijssen V, Griffioen A . The great escape; the hallmarks of resistance to antiangiogenic therapy. Pharmacol Rev. 2015; 67(2):441-61. DOI: 10.1124/pr.114.010215. View

15.

Kuhnert F, Mancuso M, Shamloo A, Wang H, Choksi V, Florek M . Essential regulation of CNS angiogenesis by the orphan G protein-coupled receptor GPR124. Science. 2010; 330(6006):985-9. PMC: 3099479. DOI: 10.1126/science.1196554. View

16.

Hamann J, Koning N, Pouwels W, Ulfman L, van Eijk M, Stacey M . EMR1, the human homolog of F4/80, is an eosinophil-specific receptor. Eur J Immunol. 2007; 37(10):2797-802. DOI: 10.1002/eji.200737553. View

17.

Rapisarda A, Melillo G . Overcoming disappointing results with antiangiogenic therapy by targeting hypoxia. Nat Rev Clin Oncol. 2012; 9(7):378-90. DOI: 10.1038/nrclinonc.2012.64. View

18.

Glade Bender J, Cooney E, Kandel J, Yamashiro D . Vascular remodeling and clinical resistance to antiangiogenic cancer therapy. Drug Resist Updat. 2004; 7(4-5):289-300. DOI: 10.1016/j.drup.2004.09.001. View

19.

Seifert J, Mlodzik M . Frizzled/PCP signalling: a conserved mechanism regulating cell polarity and directed motility. Nat Rev Genet. 2007; 8(2):126-38. DOI: 10.1038/nrg2042. View

20.

Secord A, Nixon A, Hurwitz H . The search for biomarkers to direct antiangiogenic treatment in epithelial ovarian cancer. Gynecol Oncol. 2014; 135(2):349-58. DOI: 10.1016/j.ygyno.2014.08.033. View