Notch Signaling in Regulating Angiogenesis in a 3D Biomimetic Environment

Overview

Journal Lab Chip

Publisher Royal Society of Chemistry

Specialties Biotechnology
Chemistry

Date 2017 May 5

PMID 28470301

Citations 12

Authors

Yi Zheng

Shue Wang

Xufeng Xue

Alan Xu

Wei Liao

Alice Deng

Guohao Dai

Allen P Liu

Jianping Fu

Affiliations

Soon will be listed here.

Abstract

Angiogenesis is a complex cellular process involving highly orchestrated invasion and organization of endothelial cells (ECs) in a three-dimensional (3D) environment. Recent evidence indicates that Notch signaling is critically involved in regulating specialized functions and distinct fates of ECs in newly formed vasculatures during angiogenesis. Here, we demonstrated, for the first time, the application of a microengineered biomimetic system to quantitatively investigate the role of Notch signaling in regulating early angiogenic sprouting and vasculature formation of ECs in a 3D extracellular matrix. Morphological features of angiogenesis including invasion distance, invasion area, and tip cell number were quantified and compared under pharmacological perturbations of Notch signaling. In addition, influences of Notch signaling on EC proliferation in angiogenic vasculatures and directional invasion of tip cells were also investigated. Moreover, leveraging a novel nanobiosensor system, mRNA expression of Dll4, a Notch ligand, was monitored in invading tip cells using live cell imaging during the dynamic angiogenic process. Our data showed that inhibition of Notch signaling resulted in hyper-sprouting endothelial structures, while activation of Notch signaling led to opposite effects. Our results also supported the role of Notch signaling in regulating EC proliferation and dynamic invasion of tip cells during angiogenesis.

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References

Wang S, Sun J, Zhang D, Wong P . A nanobiosensor for dynamic single cell analysis during microvascular self-organization. Nanoscale. 2016; 8(38):16894-901. PMC: 5042875. DOI: 10.1039/c6nr03907c. View

Siekmann A, Lawson N . Notch signalling limits angiogenic cell behaviour in developing zebrafish arteries. Nature. 2007; 445(7129):781-4. DOI: 10.1038/nature05577. View

Noguera-Troise I, Daly C, Papadopoulos N, Coetzee S, Boland P, Gale N . Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis. Nature. 2006; 444(7122):1032-7. DOI: 10.1038/nature05355. View

Moya I, Umans L, Maas E, Pereira P, Beets K, Francis A . Stalk cell phenotype depends on integration of Notch and Smad1/5 signaling cascades. Dev Cell. 2012; 22(3):501-14. PMC: 4544746. DOI: 10.1016/j.devcel.2012.01.007. View

Bernier-Latmani J, Cisarovsky C, Saygili Demir C, Bruand M, Jaquet M, Davanture S . DLL4 promotes continuous adult intestinal lacteal regeneration and dietary fat transport. J Clin Invest. 2015; 125(12):4572-86. PMC: 4665794. DOI: 10.1172/JCI82045. View

Stahl A, Connor K, Sapieha P, Chen J, Dennison R, Krah N . The mouse retina as an angiogenesis model. Invest Ophthalmol Vis Sci. 2010; 51(6):2813-26. PMC: 2891451. DOI: 10.1167/iovs.10-5176. View

Jakobsson L, Franco C, Bentley K, Collins R, Ponsioen B, Aspalter I . Endothelial cells dynamically compete for the tip cell position during angiogenic sprouting. Nat Cell Biol. 2010; 12(10):943-53. DOI: 10.1038/ncb2103. View

Hoey T, Yen W, Axelrod F, Basi J, Donigian L, Dylla S . DLL4 blockade inhibits tumor growth and reduces tumor-initiating cell frequency. Cell Stem Cell. 2009; 5(2):168-77. DOI: 10.1016/j.stem.2009.05.019. View

Stenzel D, Franco C, Estrach S, Mettouchi A, Sauvaget D, Rosewell I . Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo. EMBO Rep. 2011; 12(11):1135-43. PMC: 3207109. DOI: 10.1038/embor.2011.194. View

10.

Uemura A, Kusuhara S, Katsuta H, Nishikawa S . Angiogenesis in the mouse retina: a model system for experimental manipulation. Exp Cell Res. 2005; 312(5):676-83. DOI: 10.1016/j.yexcr.2005.10.030. View

11.

Roca C, Adams R . Regulation of vascular morphogenesis by Notch signaling. Genes Dev. 2007; 21(20):2511-24. DOI: 10.1101/gad.1589207. View

12.

Mak I, Evaniew N, Ghert M . Lost in translation: animal models and clinical trials in cancer treatment. Am J Transl Res. 2014; 6(2):114-8. PMC: 3902221. View

13.

Chung A, Ferrara N . Developmental and pathological angiogenesis. Annu Rev Cell Dev Biol. 2011; 27:563-84. DOI: 10.1146/annurev-cellbio-092910-154002. View

14.

Claxton S, Fruttiger M . Periodic Delta-like 4 expression in developing retinal arteries. Gene Expr Patterns. 2004; 5(1):123-7. DOI: 10.1016/j.modgep.2004.05.004. View

15.

Iso T, Hamamori Y, Kedes L . Notch signaling in vascular development. Arterioscler Thromb Vasc Biol. 2003; 23(4):543-53. DOI: 10.1161/01.ATV.0000060892.81529.8F. View

16.

Liu Z, Shirakawa T, Li Y, Soma A, Oka M, Dotto G . Regulation of Notch1 and Dll4 by vascular endothelial growth factor in arterial endothelial cells: implications for modulating arteriogenesis and angiogenesis. Mol Cell Biol. 2002; 23(1):14-25. PMC: 140667. DOI: 10.1128/MCB.23.1.14-25.2003. View

17.

Weis S, Cheresh D . Tumor angiogenesis: molecular pathways and therapeutic targets. Nat Med. 2011; 17(11):1359-70. DOI: 10.1038/nm.2537. View

18.

Jeon J, Bersini S, Gilardi M, Dubini G, Charest J, Moretti M . Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation. Proc Natl Acad Sci U S A. 2014; 112(1):214-9. PMC: 4291627. DOI: 10.1073/pnas.1417115112. View

19.

Bentley K, Franco C, Philippides A, Blanco R, Dierkes M, Gebala V . The role of differential VE-cadherin dynamics in cell rearrangement during angiogenesis. Nat Cell Biol. 2014; 16(4):309-21. DOI: 10.1038/ncb2926. View

20.

Kim S, Chung M, Jeon N . Three-dimensional biomimetic model to reconstitute sprouting lymphangiogenesis in vitro. Biomaterials. 2015; 78:115-28. DOI: 10.1016/j.biomaterials.2015.11.019. View