Angiogenic activity of breast cancer patients' monocytes reverted by combined use of systems modeling and experimental approaches

PLoS Computational Biology
Nicolas GuexMarie-Agnès Doucey

Abstract

Angiogenesis plays a key role in tumor growth and cancer progression. TIE-2-expressing monocytes (TEM) have been reported to critically account for tumor vascularization and growth in mouse tumor experimental models, but the molecular basis of their pro-angiogenic activity are largely unknown. Moreover, differences in the pro-angiogenic activity between blood circulating and tumor infiltrated TEM in human patients has not been established to date, hindering the identification of specific targets for therapeutic intervention. In this work, we investigated these differences and the phenotypic reversal of breast tumor pro-angiogenic TEM to a weak pro-angiogenic phenotype by combining Boolean modelling and experimental approaches. Firstly, we show that in breast cancer patients the pro-angiogenic activity of TEM increased drastically from blood to tumor, suggesting that the tumor microenvironment shapes the highly pro-angiogenic phenotype of TEM. Secondly, we predicted in silico all minimal perturbations transitioning the highly pro-angiogenic phenotype of tumor TEM to the weak pro-angiogenic phenotype of blood TEM and vice versa. In silico predicted perturbations were validated experimentally using patient TEM. In addition, gene e...Continue Reading

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Citations

Mar 17, 2016·BMC Research Notes·Isaac CrespoIoannis Xenarios
Oct 10, 2015·Oncoimmunology·Marie-Agnès Doucey, Ioannis Xenarios
May 17, 2018·Angiogenesis·Patrycja Nowak-SliwinskaArjan W Griffioen
May 17, 2017·Oncoimmunology·Riccardo TurriniMarie-Agnès Doucey
Nov 27, 2016·Genome Medicine·Jonathan R DryJulio Saez-Rodriguez
Apr 30, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Laura CiarloniGian Dorta
Jul 3, 2021·International Journal of Molecular Sciences·Ava J Boutilier, Sherine F Elsawa

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Datasets Mentioned

BETA
GSE34559

Methods Mentioned

BETA
flow cytometry
biopsy
FCS
Facs
protein profiling
confocal

Software Mentioned

Gene Set Enrichment Analysis ( GSEA )
Affymetrix
Bioconductor affy
Facs
Affymetrix Power Tools
R
limma
GraphPad
affyPLM
Image J

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