Summary
The tyrosine kinase system angiopoietin (Ang)/Tie interacts with vascular endothelial growth factor pathway and regulates vessel quiescence in adults as well as later steps of the angiogenic cascade related to vessel maturation. Since all Angs are able to bind to Tie-2 but none binds to Tie-1, the function of Tie-2 and its ligands have captured attention. However, emerging evidence indicates unique roles of the orphan receptor Tie-1 in angiogenesis under physiological and pathological conditions. It is required for maintaining vascular endothelial cell integrity and survival during murine embryo development and in adult and may be involved in modulating differentiation of hematopoietic cells in adult. Tie-1 exhibits poor tyrosine kinase activity and signals via forming heterodimers with Tie-2, inhibiting Tie-2 signaling mediated by Angs. This inhibition can be relieved by Tie-1 ectodomain cleavage mediated by tumor- and inflammatory-related factors, which causes destabilization of vessels and initiates vessel remodeling. Up-regulated Tie-1 expression has been found not only in some leukemia cells and tumor related endothelial cells but also in cytoplasm of carcinoma cells of a variety of human solid tumors, which is associated with tumor progression. In addition, it has pro-inflammatory functions in endothelial cells and is involved in some inflammatory diseases associated with angiogenesis. Recent research indicated that Tie-1 gene ablation exhibited significant effects on tumor blood- and lymph-angiogenesis and improved anti-Ang therapy, suggesting Tie-1 may be a potential target for tumor anti-angiogenesis treatment.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Jain RK, Carmeliet P. SnapShot: Tumor angiogenesis. Cell, 2012,149(6):1408–1408
Donnem T, Hu J, Ferguson M, et al. Vessel co-option in primary human tumors and metastases: an obstacle to effective anti-angiogenic treatment? Cancer Med, 2013,2(4):427–436
Bergers G, Hanahan D. Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer, 2008,8(8): 592- 603
Verstovsek S, Estey E, Manshouri T, et al. High expression of the receptor tyrosine kinase Tie-1 in acute myeloid leukemia and myelodysplastic syndrome. Leuk Lymphoma, 2001,42(3):511–516
Eroglu Z, Stein CA, Pal SK. Targeting angiopoietin-2 signaling in cancer therapy. Expert Opin Investig Drugs, 2013,22(7):813–825
Gerald D, Chintharlapalli S, Augustin HG, et al. Angiopoietin-2: an attractive target for improved antiangiogenic tumor therapy. Cancer Res, 2013,73(6): 1649–1657
D'Amico G, Korhonen EA, Anisimov A, et al. Tie1 deletion inhibits tumor growth and improves angiopoietin antagonist therapy. J Clin Invest, 2014,124(2):824–834
Singh H, Hansen TM, Patel N, et al. The molecular balance between receptor tyrosine kinases Tie1 and Tie2 is dynamically controlled by VEGF and TNFalpha and regulates angiopoietin signalling. PLoS One, 2012,7(1): e29319
Augustin HG, Koh GY, Thurston G, et al. Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nat Rev Mol Cell Biol, 2009,10(3):165–177
Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature, 2011,473(7347): 298–307
Fagiani E, Christofori G. Angiopoietins in angiogenesis. Cancer Lett, 2013,328(1):18–26
Lee HJ, Cho CH, Hwang SJ, et al. Biological characterization of angiopoietin-3 and angiopoietin-4. FASEB J, 2004,18(11):1200–1208
Brunckhorst MK, Wang H, Lu R, et al. Angiopoietin-4 promotes glioblastoma progression by enhancing tumor cell viability and angiogenesis. Cancer Res, 2010,70(18): 7283–7293
Kim KL, Shin IS, Kim JM, et al. Interaction between Tie receptors modulates angiogenic activity of angiopoietin2 in endothelial progenitor cells. Cardiovasc Res, 2006,72(3):394–402
Seegar TC, Eller B, Tzvetkova-Robev D, et al. Tie1-Tie2 interactions mediate functional differences between angiopoietin ligands. Mol Cell, 2010,37(5):643–655
Song SH, Kim KL, Lee KA, et al. Tie1 regulates the Tie2 agonistic role of angiopoietin-2 in human lymphatic endothelial cells. Biochem Biophys Res Commun, 2012,419(2):281–286
Woo KV, Baldwin HS. Role of Tie1 in shear stress and atherosclerosis. Trends Cardiovasc Med 2011,21(4): 118–123
Yuan HT, Venkatesha S, Chan B, et al. Activation of the orphan endothelial receptor Tie1 modifies Tie2-mediated intracellular signaling and cell survival. FASEB J, 2007,21(12):3171–3183
Partanen J, Armstrong E, Makela TP, et al. A novel endothelial cell surface receptor tyrosine kinase with extracellular epidermal growth factor homology domains. Mol Cell Biol, 1992,12(4):1698–1707
Dumont DJ, Gradwohl GJ, Fong GH, et al. The endothelial-specific receptor tyrosine kinase, tek, is a member of a new subfamily of receptors. Oncogene, 1993,8(5):1293–1301
Yabkowitz R, Meyer S, Yanagihara D, et al. Regulation of tie receptor expression on human endothelial cells by protein kinase C-mediated release of soluble tie. Blood, 1997,90(2):706–715
Hansen TM, Singh H, Tahir TA, et al. Effects of angiopoietins-1 and -2 on the receptor tyrosine kinase Tie2 are differentially regulated at the endothelial cell surface. Cell Signal, 2010,22(3):527–532
Korhonen J, Partanen J, Armstrong E, et al. Enhanced expression of the tie receptor tyrosine kinase in endothelial cells during neovascularization. Blood, 1992,80(10):2548–2555
Korhonen J, Polvi A, Partanen J, et al. The mouse tie receptor tyrosine kinase gene: expression during embryonic angiogenesis. Oncogene, 1994,9(2):395–403
Sato TN, Tozawa Y, Deutsch U, et al. Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation. Nature, 1995,376(6535):70–74
Porat RM, Grunewald M, Globerman A, et al. Specific induction of tie1 promoter by disturbed flow in atherosclerosis-prone vascular niches and flow-obstructing pathologies. Circ Res, 2004,94(3):394–401
D'Amico G, Korhonen EA, Waltari M, et al. Loss of endothelial Tie1 receptor impairs lymphatic vessel development-brief report. Arterioscler Thromb Vasc Biol, 2010,30(2):207–209
Puri MC, Rossant J, Alitalo K, et al. The receptor tyrosine kinase TIE is required for integrity and survival of vascular endothelial cells. EMBO J, 1995,14(23): 5884–5891
Puri MC, Partanen J, Rossant J, et al. Interaction of the TEK and TIE receptor tyrosine kinases during cardiovascular development. Development, 1999,126(20): 4569–4580
Partanen J, Puri MC, Schwartz L, et al. Cell autonomous functions of the receptor tyrosine kinase TIE in a late phase of angiogenic capillary growth and endothelial cell survival during murine development. Development, 1996,122(10):3013–3021
Puri MC, Bernstein A. Requirement for the TIE family of receptor tyrosine kinases in adult but not fetal hematopoiesis. Proc Natl Acad Sci U S A, 2003,100(22):12753–12758
Patan S. TIE1 and TIE2 receptor tyrosine kinases inversely regulate embryonic angiogenesis by the mechanism of intussusceptive microvascular growth. Microvasc Res, 1998,56(1):1–21
Argraves WS, Larue AC, Fleming PA, et al. VEGF signaling is required for the assembly but not the maintenance of embryonic blood vessels. Dev Dyn, 2002,225(3):298–304
Batard P, Sansilvestri P, Scheinecker C, et al. The Tie receptor tyrosine kinase is expressed by human hematopoietic progenitor cells and by a subset of megakaryocytic cells. Blood, 1996,87(6):2212–2220
Hashiyama M, Iwama A, Ohshiro K, et al. Predominant expression of a receptor tyrosine kinase, TIE, in hematopoietic stem cells and B cells. Blood, 1996,87(1):93–101
Marron MB, Singh H, Tahir TA, et al. Regulated proteolytic processing of Tie1 modulates ligand responsiveness of the receptor-tyrosine kinase Tie2. J Biol Chem, 2007,282(42):30509–30517
Saharinen P, Kerkela K, Ekman N, et al. Multiple angiopoietin recombinant proteins activate the Tie1 receptor tyrosine kinase and promote its interaction with Tie2. J Cell Biol, 2005,169(2):239–243
Bach F, Uddin FJ, Burke D. Angiopoietins in malignancy. Eur J Surg Oncol, 2007,33(1):7–15
Law AL, Parinot C, Chatagnon J, et al. Cleavage of Mer tyrosine kinase (MerTK) from the cell surface contributes to the regulation of retinal phagocytosis. J Biol Chem, 2014,290(8):4941–4952
Marron MB, Hughes DP, Mc Carthy MJ, et al. Tie-1 receptor tyrosine kinase endodomain interaction with SHP2: potential signalling mechanisms and roles in angiogenesis. Adv Exp Med Biol, 2000,476:35–46
Qu CK. The SHP-2 tyrosine phosphatase: signaling mechanisms and biological functions. Cell Res, 2000,10(4):279–288
Armstrong E, Korhonen J, Silvennoinen O, et al. Expression of tie receptor tyrosine kinase in leukemia cell lines. Leukemia, 1993,7(10):1585–1591
Kivivuori SM, Siitonen S, Porkka K, et al. Expression of vascular endothelial growth factor receptor 3 and Tie1 tyrosine kinase receptor on acute leukemia cells. Pediatr Blood Cancer, 2007,48(4):387–392
Verstovsek S, Kantarjian H, Manshouri T, et al. Prognostic significance of Tie-1 protein expression in patients with early chronic phase chronic myeloid leukemia. Cancer, 2002,94(5):1517–1521
Qiu S, Jia Y, Xing H, et al. N-Cadherin and Tie2 positive CD34(+)CD38(-)CD123(+) leukemic stem cell populations can develop acute myeloid leukemia more effectively in NOD/SCID mice. Leuk Res, 2014,38(5): 632–637
Salven P, Joensuu H, Heikkila P, et al. Endothelial Tie growth factor receptor provides antigenic marker for assessment of breast cancer angiogenesis. Br J Cancer, 1996,74(1):69–72
Ito Y, Yoshida H, Uruno T, et al. Tie-1 tyrosine kinase expression in human thyroid neoplasms. Histopathology, 2004,44(4):318–322
Buehler D, Rush P, Hasenstein JR, et al. Expression of angiopoietin-TIE system components in angiosarcoma. Mod Pathol, 2013,26(8):1032–1040
Rees KA, Singh H, Brindle NP. The receptor tyrosine kinase Tie1 is expressed and activated in epithelial tumour cell lines. Int J Oncol, 2007,31(4):893–897
Fukuhara S, Sako K, Minami T, et al. Differential function of Tie2 at cell-cell contacts and cell-substratum contacts regulated by angiopoietin-1. Nat Cell Biol, 2008,10(5): 513–526
Fukuhara S, Sako K, Noda K, et al. Angiopoietin-1/Tie2 receptor signaling in vascular quiescence and angiogenesis. Histol Histopathol, 2010,25(3):387–396
Garcia A, Kandel JJ. Notch: a key regulator of tumor angiogenesis and metastasis. Histol Histopathol, 2012, 27(2):151–156
Potenta S, Zeisberg E, Kalluri R. The role of endothelial-to-mesenchymal transition in cancer progression. Br J Cancer, 2008,99(9):1375–1379
Zeisberg EM, Potenta S, Xie L, et al. Discovery of endothelial to mesenchymal transition as a source for carcinoma-associated fibroblasts. Cancer Res, 2007,67(21): 10123–10128
Garcia J, Sandi MJ, Cordelier P, et al. Tie1 deficiency induces endothelial-mesenchymal transition. EMBO Rep, 2012,13(5):431–439
Jin P, Zhang J, Sumariwalla PF, et al. Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis. Arthritis Res Ther, 2008,10(4):R73
Chan B, Sukhatme VP. Suppression of Tie-1 in endothelial cells in vitro induces a change in the genome-wide expression profile reflecting an inflammatory function. FEBS Lett, 2009,583(6):1023–1028
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell, 2011,144(5):646–674
Kaipainen A, Vlaykova T, Hatva E, et al. Enhanced expression of the tie receptor tyrosine kinase mesenger RNA in the vascular endothelium of metastatic melanomas. Cancer Res, 1994,54(24):6571–6577
Chan B, Yuan HT, Ananth Karumanchi S, et al. Receptor tyrosine kinase Tie-1 overexpression in endothelial cells upregulates adhesion molecules. Biochem Biophys Res Commun, 2008,371(3):475–479
Che CL, Zhang YM, Zhang HH, et al. DNA microarray reveals different pathways responding to paclitaxel and docetaxel in non-small cell lung cancer cell line. Int J Clin Exp Pathol, 2013,6(8):1538–1548
Li K, Blum Y, Verma A, et al. A noncoding antisense RNA in tie-1 locus regulates tie-1 function in vivo. Blood, 2010,115(1):133–139
Xing Z, Li D, Yang L, et al. MicroRNAs and anticancer drugs. Acta Biochim Biophys Sin (Shanghai), 2014,46(3): 233–239
Author information
Authors and Affiliations
Corresponding authors
Additional information
This project was supported by grants from the Fundamental Research Funds for the Central Universities (HUST: 2015ZHYX015) and the National Natural Science Foundation of China (No. 81272860).
Rights and permissions
About this article
Cite this article
Yang, P., Chen, N., Jia, Jh. et al. Tie-1: A potential target for anti-angiogenesis therapy. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 35, 615–622 (2015). https://doi.org/10.1007/s11596-015-1479-1
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11596-015-1479-1