Effects of Endothelial Cell Proliferation and Migration Rates in a Computational Model of Sprouting Angiogenesis

Overview

Journal Sci Rep

Specialty Science

Date 2016 Nov 15

PMID 27841344

Citations 74

Authors

Kerri-Ann Norton

Aleksander S Popel

Affiliations

Soon will be listed here.

Abstract

Angiogenesis, the recruitment of new blood vessels, is a critical process for the growth, expansion, and metastatic dissemination of developing tumors. Three types of cells make up the new vasculature: tip cells, which migrate in response to gradients of vascular endothelial growth factor (VEGF), stalk cells, which proliferate and extend the vessels, and phalanx cells, which are quiescent and support the sprout. In this study we examine the contribution of tip cell migration rate and stalk cell proliferation rate on the formation of new vasculature. We calculate several vascular metrics, such as the number of vascular bifurcations per unit volume, vascular segment length per unit volume, and vascular tortuosity. These measurements predict that proliferation rate has a greater effect on the spread and extent of vascular growth compared to migration rate. Together, these findings provide strong implications for designing anti-angiogenic therapies that may differentially target endothelial cell proliferation and migration. Computational models can be used to predict optimal anti-angiogenic therapies in combination with other therapeutics to improve outcome.

Citing Articles

Peptide Lv and Angiogenesis: A Newly Discovered Angiogenic Peptide.

Pham D, Cox K, Ko M, Ko G Biomedicines. 2025; 12(12.

PMID: 39767758 PMC: 11672992. DOI: 10.3390/biomedicines12122851.

Glioblastoma cells alter brain endothelial cell homeostasis and tight junction protein expression in vitro.

Mokoena X, Mabeta P, Cordier W, Flepisi B J Neurooncol. 2024; 171(2):443-453.

PMID: 39538037 PMC: 11695387. DOI: 10.1007/s11060-024-04870-5.

Effect of snail mucus on angiogenesis during wound healing.

Rosanto Y, Hasan C, Rahardjo R, Pangestiningsih T F1000Res. 2024; 10:181.

PMID: 38912381 PMC: 11190653. DOI: 10.12688/f1000research.51297.2.

The Effects of Preeclamptic Milieu on Cord Blood Derived Endothelial Colony-Forming Cells.

Hall E, Alderfer L, Neu E, Saha S, Johandes E, Haas D bioRxiv. 2023; .

PMID: 38105991 PMC: 10723349. DOI: 10.1101/2023.12.03.569585.

Cracking the Endothelial Calcium (Ca) Code: A Matter of Timing and Spacing.

Moccia F, Brunetti V, Soda T, Berra-Romani R, Scarpellino G Int J Mol Sci. 2023; 24(23).

PMID: 38069089 PMC: 10706333. DOI: 10.3390/ijms242316765.

References

Milde F, Bergdorf M, Koumoutsakos P . A hybrid model for three-dimensional simulations of sprouting angiogenesis. Biophys J. 2008; 95(7):3146-60. PMC: 2547461. DOI: 10.1529/biophysj.107.124511. View

Vilanova G, Colominas I, Gomez H . Capillary networks in tumor angiogenesis: from discrete endothelial cells to phase-field averaged descriptions via isogeometric analysis. Int J Numer Method Biomed Eng. 2013; 29(10):1015-37. DOI: 10.1002/cnm.2552. View

Vempati P, Popel A, Mac Gabhann F . Extracellular regulation of VEGF: isoforms, proteolysis, and vascular patterning. Cytokine Growth Factor Rev. 2013; 25(1):1-19. PMC: 3977708. DOI: 10.1016/j.cytogfr.2013.11.002. View

Lee E, Koskimaki J, Pandey N, Popel A . Inhibition of lymphangiogenesis and angiogenesis in breast tumor xenografts and lymph nodes by a peptide derived from transmembrane protein 45A. Neoplasia. 2013; 15(2):112-24. PMC: 3579314. DOI: 10.1593/neo.121638. View

Claesson-Welsh L, Welsh M . VEGFA and tumour angiogenesis. J Intern Med. 2012; 273(2):114-27. DOI: 10.1111/joim.12019. View

Norton K, Popel A, Pandey N . Heterogeneity of chemokine cell-surface receptor expression in triple-negative breast cancer. Am J Cancer Res. 2015; 5(4):1295-307. PMC: 4473311. View

Goel S, Wong A, Jain R . Vascular normalization as a therapeutic strategy for malignant and nonmalignant disease. Cold Spring Harb Perspect Med. 2012; 2(3):a006486. PMC: 3282493. DOI: 10.1101/cshperspect.a006486. View

Tan W, Popel A, Mac Gabhann F . Computational Model of Gab1/2-Dependent VEGFR2 Pathway to Akt Activation. PLoS One. 2013; 8(6):e67438. PMC: 3689841. DOI: 10.1371/journal.pone.0067438. View

Thurston G, Noguera-Troise I, Yancopoulos G . The Delta paradox: DLL4 blockade leads to more tumour vessels but less tumour growth. Nat Rev Cancer. 2007; 7(5):327-31. DOI: 10.1038/nrc2130. View

10.

Frye C, Patrick Jr C . Isolation and culture of rat microvascular endothelial cells. In Vitro Cell Dev Biol Anim. 2002; 38(4):208-12. DOI: 10.1290/1071-2690(2002)038<0208:IACORM>2.0.CO;2. View

11.

Santos-Oliveira P, Correia A, Rodrigues T, Ribeiro-Rodrigues T, Matafome P, Rodriguez-Manzaneque J . The Force at the Tip--Modelling Tension and Proliferation in Sprouting Angiogenesis. PLoS Comput Biol. 2015; 11(8):e1004436. PMC: 4527825. DOI: 10.1371/journal.pcbi.1004436. View

12.

Liu G, Qutub A, Vempati P, Mac Gabhann F, Popel A . Module-based multiscale simulation of angiogenesis in skeletal muscle. Theor Biol Med Model. 2011; 8:6. PMC: 3079676. DOI: 10.1186/1742-4682-8-6. View

13.

Kim M, Gillies R, Rejniak K . Current advances in mathematical modeling of anti-cancer drug penetration into tumor tissues. Front Oncol. 2013; 3:278. PMC: 3831268. DOI: 10.3389/fonc.2013.00278. View

14.

Gacche R, Meshram R . Angiogenic factors as potential drug target: efficacy and limitations of anti-angiogenic therapy. Biochim Biophys Acta. 2014; 1846(1):161-79. DOI: 10.1016/j.bbcan.2014.05.002. View

15.

Chung A, Lee J, Ferrara N . Targeting the tumour vasculature: insights from physiological angiogenesis. Nat Rev Cancer. 2010; 10(7):505-14. DOI: 10.1038/nrc2868. View

16.

Karagiannis E, Popel A . Distinct modes of collagen type I proteolysis by matrix metalloproteinase (MMP) 2 and membrane type I MMP during the migration of a tip endothelial cell: insights from a computational model. J Theor Biol. 2005; 238(1):124-45. DOI: 10.1016/j.jtbi.2005.05.020. View

17.

Magdoom K, Pishko G, Rice L, Pampo C, Siemann D, Sarntinoranont M . MRI-based computational model of heterogeneous tracer transport following local infusion into a mouse hind limb tumor. PLoS One. 2014; 9(3):e89594. PMC: 3949671. DOI: 10.1371/journal.pone.0089594. View

18.

Folkman J . Angiogenesis: an organizing principle for drug discovery?. Nat Rev Drug Discov. 2007; 6(4):273-86. DOI: 10.1038/nrd2115. View

19.

Finley S, Popel A . Predicting the effects of anti-angiogenic agents targeting specific VEGF isoforms. AAPS J. 2012; 14(3):500-9. PMC: 3385824. DOI: 10.1208/s12248-012-9363-4. View

20.

Vasudev N, Reynolds A . Anti-angiogenic therapy for cancer: current progress, unresolved questions and future directions. Angiogenesis. 2014; 17(3):471-94. PMC: 4061466. DOI: 10.1007/s10456-014-9420-y. View