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Title

Angiogenic factor-driven inflammation promotes extravasation of human proangiogenic monocytes to tumours

Authors
Pocard, Marc
Published in Nature Communications. 2018, vol. 9, no. 1, p. 19
Abstract Recruitment of circulating monocytes is critical for tumour angiogenesis. However, how human monocyte subpopulations extravasate to tumours is unclear. Here we show mechanisms of extravasation of human CD14dimCD16+ patrolling and CD14+CD16+ intermediate proangiogenic monocytes (HPMo), using human tumour xenograft models and live imaging of transmigration. IFNγ promotes an increase of the chemokine CX3CL1 on vessel lumen, imposing continuous crawling to HPMo and making these monocytes insensitive to chemokines required for their extravasation. Expression of the angiogenic factor VEGF and the inflammatory cytokine TNF by tumour cells enables HPMo extravasation by inducing GATA3-mediated repression of CX3CL1 expression. Recruited HPMo boosts angiogenesis by secreting MMP9 leading to release of matrix-bound VEGF-A, which amplifies the entry of more HPMo into tumours. Uncovering the extravasation cascade of HPMo sets the stage for future tumour therapies.
Keywords AngiogenesisMonocyteChemokineMigrationCancerColorectalBreast: inflammationSeinNon-classicalLeukocytePatrolling
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Other version: http://www.nature.com/articles/s41467-017-02610-0
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Project FNS: 310030_153456
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SIDIBE, Adama et al. Angiogenic factor-driven inflammation promotes extravasation of human proangiogenic monocytes to tumours. In: Nature Communications, 2018, vol. 9, n° 1, p. 19. https://archive-ouverte.unige.ch/unige:106130

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Deposited on : 2018-07-04

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