Suppression of β3-integrin in mice triggers a neuropilin-1- dependent change in focal adhesion remodelling that can be targeted to block pathological angiogenesis

DMM Disease Models and Mechanisms

Volumn 8, Issue 9, 2015, Pages 1105-1119

  Ellison, Tim S ^a   Atkinson, Samuel J ^a   Steri, Veronica ^a   Kirkup, Benjamin M ^a   Preedy, Michael E J ^a   Johnson, Robert T ^a   Ruhrberg, Christiana ^b   Edwards, Dylan R ^a   Schneider, Jochen G ^c   Weilbaecher, Katherine ^d   Robinson, Stephen D ^a  

^a UNIVERSITY OF EAST ANGLIA   (United Kingdom)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

^c SAARLAND UNIVERSITY   (Germany)

^d WASHINGTON UNIVERSITY   (United States)

Author keywords

Angiogenesis; Focal adhesion; Integrin; Neuropilin 1; Tumour

Indexed keywords

BETA3 INTEGRIN; NEUROPILIN 1; PAXILLIN; PAXILLIN 1; UNCLASSIFIED DRUG; VASCULOTROPIN; INTEGRIN; KDR PROTEIN, MOUSE; PXN PROTEIN, MOUSE; VASCULOTROPIN A; VASCULOTROPIN RECEPTOR 2;

ADVANCED CANCER; ANGIOGENESIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIANGIOGENIC THERAPY; ARTICLE; CELL MIGRATION; CONTROLLED STUDY; ENDOTHELIUM CELL; FOCAL ADHESION; GENE TARGETING; MOUSE; NONHUMAN; PRIORITY JOURNAL; ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; CANCER TRANSPLANTATION; CELL ADHESION; CYTOLOGY; CYTOPLASM; CYTOSKELETON; EXPERIMENTAL MELANOMA; FLOW CYTOMETRY; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETICS; HETEROZYGOTE; HUMAN; LUNG; METABOLISM; MICROCIRCULATION; NEOVASCULARIZATION (PATHOLOGY); PATHOPHYSIOLOGY; TRANSGENIC MOUSE;

ANIMALS; CELL ADHESION; CYTOPLASM; CYTOSKELETON; ENDOTHELIAL CELLS; FLOW CYTOMETRY; FOCAL ADHESIONS; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; HETEROZYGOTE; HUMANS; INTEGRIN BETA3; INTEGRINS; LUNG; MELANOMA, EXPERIMENTAL; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MICROCIRCULATION; NEOPLASM TRANSPLANTATION; NEOVASCULARIZATION, PATHOLOGIC; NEUROPILIN-1; PAXILLIN; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2;

EID: 84941564643     PISSN: 17548403     EISSN: 17548411     Source Type: Journal    
DOI: 10.1242/dmm.019927     Document Type: Article

References (54)

1. Baker, M., Robinson, S. D., Lechertier, T., Barber, P. R., Tavora, B., D'Amico, G., Jones, D. T., Vojnovic, B. and Hodivala-Dilke, K. (2012). Use of the mouse aortic ring assay to study angiogenesis. Nat. Protoc. 7, 89-104.
2. Ballmer-Hofer, K., Andersson, A. E., Ratcliffe, L. E. and Berger, P. (2011). Neuropilin-1 promotes VEGFR-2 trafficking through Rab11 vesicles thereby specifying signal output. Blood 118, 816-826.
3. Brooks, P. C., Montgomery, A. M. P., Rosenfeld, M., Reisfeld, R. A., Hu, T., Klier, G. and Cheresh, D. A. (1994). Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell 79, 1157-1164.
4. Cai, H. and Reed, R. R. (1999). Cloning and characterization of neuropilin-1-interacting protein: a PSD-95/Dlg/ZO-1 domain-containing protein that interacts with the cytoplasmic domain of neuropilin-1. J. Neurosci. 19, 6519-6527.
5. Clark, R. A., Mason, R. J., Folkvord, J. M. and McDonald, J. A. (1986). Fibronectin mediates adherence of rat alveolar type II epithelial cells via the fibroblastic cellattachment domain. J. Clin. Invest. 77, 1831-1840.
6. Claxton, S., Kostourou, V., Jadeja, S., Chambon, P., Hodivala-Dilke, K. and Fruttiger, M. (2008). Efficient, inducible Cre-recombinase activation in vascular endothelium. Genesis 46, 74-80.
7. Ebos, J. M. L. and Kerbel, R. S. (2011). Antiangiogenic therapy: impact on invasion, disease progression, and metastasis. Nat. Rev. Clin. Oncol. 8, 210-221.
8. Evans, I. M., Yamaji, M., Britton, G., Pellet-Many, C., Lockie, C., Zachary, I. C. and Frankel, P. (2011). Neuropilin-1 signaling through p130Cas tyrosine phosphorylation is essential for growth factor-dependent migration of glioma and endothelial cells. Mol. Cell. Biol. 31, 1174-1185.
9. Ewan, L. C., Jopling, H. M., Jia, H., Mittar, S., Bagherzadeh, A., Howell, G. J., Walker, J. H., Zachary, I. C. and Ponnambalam, S. (2006). Intrinsic tyrosine kinase activity is required for vascular endothelial growth factor receptor 2 ubiquitination, sorting and degradation in endothelial cells. Traffic 7, 1270-1282.
10. Fantin, A., Schwarz, Q., Davidson, K., Normando, E. M., Denti, L. and Ruhrberg, C. (2011). The cytoplasmic domain of neuropilin 1 is dispensable for angiogenesis, but promotes the spatial separation of retinal arteries and veins. Development 138, 4185-4191.
11. Fantin, A., Vieira, J. M., Plein, A., Denti, L., Fruttiger, M., Pollard, J. W. and Ruhrberg, C. (2013). NRP1 acts cell autonomously in endothelium to promote tip cell function during sprouting angiogenesis. Blood 121, 2352-2362.
12. Fantin, A., Herzog, B., Mahmoud, M., Yamaji, M., Plein, A., Denti, L., Ruhrberg, C. and Zachary, I. (2014). Neuropilin 1 (NRP1) hypomorphism combined with defective VEGF-A binding reveals novel roles for NRP1 in developmental and pathological angiogenesis. Development 141, 556-562.
13. Fukasawa, M., Matsushita, A. and Korc, M. (2007). Neuropilin-1 interacts with integrin beta1 and modulates pancreatic cancer cell growth, survival and invasion. Cancer Biol. Ther. 6, 1184-1191.
14. Gerhardt, H., Ruhrberg, C., Abramsson, A., Fujisawa, H., Shima, D. and Betsholtz, C. (2004). Neuropilin-1 is required for endothelial tip cell guidance in the developing central nervous system. Dev. Dyn. 231, 503-509.
15. Gu, C., Rodriguez, E. R., Reimert, D. V., Shu, T., Fritzsch, B., Richards, L. J., Kolodkin, A. L. and Ginty, D. D. (2003). Neuropilin-1 conveys semaphorin and VEGF signaling during neural and cardiovascular development. Dev. Cell 5, 45-57.
16. Hanahan, D. andWeinberg, R. A. (2011). Hallmarks of cancer: the next generation. Cell 144, 646-674.
17. Hariharan, S., Gustafson, D., Holden, S., McConkey, D., Davis, D., Morrow, M., Basche, M., Gore, L., Zang, C., O'Bryant, C. L. et al. (2007). Assessment of the biological and pharmacological effects of the alpha nu beta3 and alpha nu beta5 integrin receptor antagonist, cilengitide (EMD 121974), in patients with advanced solid tumors. Ann. Oncol. 18, 1400-1407.
18. Herzog, B., Pellet-Many, C., Britton, G., Hartzoulakis, B. and Zachary, I. C. (2011). VEGF binding to Neuropilin-1 (NRP1) is essential for VEGF stimulation of endothelial cell migration, complex formation between NRP1 and VEGFR2, and signaling via FAK Tyr407 phosphorylation. Mol. Biol. Cell 22, 2766-2776.
19. Hynes, R. O. (2002). Integrins: bidirectional, allosteric signaling machines. Cell 110, 673-687.
20. Kawasaki, T., Kitsukawa, T., Bekku, Y., Matsuda, Y., Sanbo, M., Yagi, T. and Fujisawa, H. (1999). A requirement for neuropilin-1 in embryonic vessel formation. Development 126, 4895-4902.
21. Koch, S., Tugues, S., Li, X., Gualandi, L. and Claesson-Welsh, L. (2011). Signal transduction by vascular endothelial growth factor receptors. Biochem. J. 437, 169-183.
22. Krilleke, D., DeErkenez, A., Schubert, W., Giri, I., Robinson, G. S., Ng, Y.-S. and Shima, D. T. (2007). Molecular mapping and functional characterization of the VEGF164 heparin-binding domain. J. Biol. Chem. 282, 28045-28056.
23. Kuo, J.-C., Han, X., Hsiao, C.-T., Yates, J. R., III and Waterman, C. M. (2011). Analysis of the myosin-II-responsive focal adhesion proteome reveals a role forbeta-Pix in negative regulation of focal adhesion maturation. Nat. Cell Biol. 13, 383-393.
24. Lampugnani, M. G., Orsenigo, F., Gagliani, M. C., Tacchetti, C. and Dejana, E. (2006). Vascular endothelial cadherin controls VEGFR-2 internalization and signaling from intracellular compartments. J. Cell Biol. 174, 593-604.
25. Lanahan, A., Zhang, X., Fantin, A., Zhuang, Z., Rivera-Molina, F., Speichinger, K., Prahst, C., Zhang, J., Wang, Y., Davis, G. et al. (2013). The neuropilin 1 cytoplasmic domain is required for VEGF-A-dependent arteriogenesis. Dev. Cell 25, 156-168.
26. Mahabeleshwar, G. H., Feng, W., Reddy, K., Plow, E. F. and Byzova, T. V. (2007). Mechanisms of integrin vascular endothelial growth factor receptor crossactivation in angiogenesis. Circ. Res. 101, 570-580.
27. Marelli, U. K., Rechenmacher, F., Sobahi, T. R. A., Mas-Moruno, C. and Kessler, H. (2013). Tumor targeting via integrin ligands. Front. Oncol. 3, 222.
28. May, T., Mueller, P. P., Weich, H., Froese, N., Deutsch, U., Wirth, D., Kroger, A. and Hauser, H. (2005). Establishment of murine cell lines by constitutive and conditional immortalization. J. Biotechnol. 120, 99-110.
29. Murga, M., Fernandez-Capetillo, O. and Tosato, G. (2005). Neuropilin-1 regulates attachment in human endothelial cells independently of vascular endothelial growth factor receptor-2. Blood 105, 1992-1999.
30. Ni, C.-W., Kumar, S., Ankeny, C. J. and Jo, H. (2014). Development of immortalized mouse aortic endothelial cell lines. Vasc. Cell 6, 7.
31. Pan, Q., Chanthery, Y., Liang, W.-C., Stawicki, S., Mak, J., Rathore, N., Tong, R. K., Kowalski, J., Yee, S. F., Pacheco, G. et al. (2007). Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth. Cancer Cell 11, 53-67.
32. Prahst, C., Heroult, M., Lanahan, A. A., Uziel, N., Kessler, O., Shraga-Heled, N., Simons, M., Neufeld, G. and Augustin, H. G. (2008). Neuropilin-1-VEGFR-2 complexing requires the PDZ-binding domain of neuropilin-1. J. Biol. Chem. 283, 25110-25114.
33. Raimondi, C., Fantin, A., Lampropoulou, A., Denti, L., Chikh, A. and Ruhrberg, C. (2014). Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1-dependent ABL1 activation in endothelial cells. J. Exp. Med. 211, 1167-1183.
34. Reynolds, L. E. and Hodivala-Dilke, K. M. (2006). Primary mouse endothelial cell culture for assays of angiogenesis. Methods Mol. Med. 120, 503-509.
35. Reynolds, L. E., Wyder, L., Lively, J. C., Taverna, D., Robinson, S. D., Huang, X., Sheppard, D., Hynes, R. O. and Hodivala-Dilke, K. M. (2002). Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins. Nat. Med. 8, 27-34.
36. Reynolds, A. R., Reynolds, L. E., Nagel, T. E., Lively, J. C., Robinson, S. D., Hicklin, D. J., Bodary, S. C. and Hodivala-Dilke, K. M. (2004). Elevated Flk1 (vascular endothelial growth factor receptor 2) signaling mediates enhanced angiogenesis in beta3-integrin-deficient mice. Cancer Res. 64, 8643-8650.
37. Reynolds, A. R., Hart, I. R., Watson, A. R., Welti, J. C., Silva, R. G., Robinson, S. D., Da Violante, G., Gourlaouen, M., Salih, M., Jones, M. C. et al. (2009). Stimulation of tumor growth and angiogenesis by low concentrations of RGDmimetic integrin inhibitors. Nat. Med. 15, 392-400.
38. Robinson, S. D. and Hodivala-Dilke, K. M. (2011). The role of beta3-integrins in tumor angiogenesis: context is everything. Curr. Opin. Cell Biol. 23, 630-637.
39. Robinson, S. D., Reynolds, L. E., Kostourou, V., Reynolds, A. R., da Silva, R. G., Tavora, B., Baker, M., Marshall, J. F. and Hodivala-Dilke, K. M. (2009). Alphav beta3 integrin limits the contribution of neuropilin-1 to vascular endothelial growth factor-induced angiogenesis. J. Biol. Chem. 284, 33966-33981.
40. Schiller, H. B., Friedel, C. C., Boulegue, C. and Fassler, R. (2011). Quantitative proteomics of the integrin adhesome show a myosin II-dependent recruitment of LIM domain proteins. EMBO Rep. 12, 259-266.
41. Schiller, H. B., Hermann, M.-R., Polleux, J., Vignaud, T., Zanivan, S., Friedel, C. C., Sun, Z., Raducanu, A., Gottschalk, K.-E., Thery, M. et al. (2013). beta1-and alphav-class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin-based microenvironments. Nat. Cell Biol. 15, 625-636.
42. Seerapu, H. R., Borthakur, S., Kong, N., Agrawal, S., Drazba, J., Vasanji, A., Fantin, A., Ruhrberg, C., Buck, M. and Horowitz, A. (2013). The cytoplasmic domain of neuropilin-1 regulates focal adhesion turnover. FEBS Lett. 587, 3392-3399.
43. Sennino, B. and McDonald, D. M. (2012). Controlling escape from angiogenesis inhibitors. Nat. Rev. Cancer 12, 699-709.
44. Silva, R., D'Amico, G., Hodivala-Dilke, K. M. and Reynolds, L. E. (2008). Integrins: the keys to unlocking angiogenesis. Arterioscler. Thromb. Vasc. Biol. 28, 1703-1713.
45. Soldi, R., Mitola, S., Strasly, M., Defilippi, P., Tarone, G. and Bussolino, F. (1999). Role of alphavbeta3 integrin in the activation of vascular endothelial growth factor receptor-2. EMBO J. 18, 882-892.
46. Sottile, J., Hocking, D. C. and Swiatek, P. J. (1998). Fibronectin matrix assembly enhances adhesion-dependent cell growth. J. Cell Sci. 111, 2933-2943.
47. Steri, V., Ellison, T. S., Gontarczyk, A. M., Weilbaecher, K., Schneider, J. G., Edwards, D., Fruttiger, M., Hodivala-Dilke, K. M. and Robinson, S. D. (2014). Acute depletion of endothelial beta3-integrin transiently inhibits tumor growth and angiogenesis in mice. Circ. Res. 114, 79-91.
48. Takagi, S., Kasuya, Y., Shimizu, M., Matsuura, T., Tsuboi, M., Kawakami, A. and Fujisawa, H. (1995). Expression of a cell adhesion molecule, neuropilin, in the developing chick nervous system. Dev. Biol. 170, 207-222.
49. Tavora, B., Reynolds, L. E., Batista, S., Demircioglu, F., Fernandez, I., Lechertier, T., Lees, D. M., Wong, P.-P., Alexopoulou, A., Elia, G. et al. (2014). Endothelial-cell FAK targeting sensitizes tumours to DNA-damaging therapy. Nature 514, 112-116.
50. Truong, H. and Danen, E. H. J. (2009). Integrin switching modulates adhesion dynamics and cell migration. Cell Adh. Migr. 3, 179-181.
51. Tvorogov, D., Wang, X.-J., Zent, R. and Carpenter, G. (2005). Integrin-dependent PLC-gamma1 phosphorylation mediates fibronectin-dependent adhesion. J. Cell Sci. 118, 601-610.
52. Valdembri, D., Caswell, P. T., Anderson, K. I., Schwarz, J. P., Konig, I., Astanina, E., Caccavari, F., Norman, J. C., Humphries, M. J., Bussolino, F. et al. (2009). Neuropilin-1/GIPC1 signaling regulates alpha5beta1 integrin traffic and function in endothelial cells. PLoS Biol. 7, e25.
53. Zamir, E. and Geiger, B. (2001). Molecular complexity and dynamics of cell-matrix adhesions. J. Cell Sci. 114, 3583-3590.
54. Zamir, E., Katz, M., Posen, Y., Erez, N., Yamada, K. M., Katz, B. Z., Lin, S., Lin, D. C., Bershadsky, A., Kam, Z. et al. (2000). Dynamics and segregation of cellmatrix adhesions in cultured fibroblasts. Nat. Cell Biol. 2, 191-196.