Angiogenic factor-driven inflammation promotes extravasation of human proangiogenic monocytes to tumours
Autor: | Marine Poittevin, Patricia Ropraz, Yalin Emre, Paul F. Bradfield, Adama Sidibé, Marc Pocard, Stephane Jemelin, Beat A. Imhof |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Vascular Endothelial Growth Factor A Chemokine Angiogenesis medicine.medical_treatment General Physics and Astronomy Mice SCID ddc:616.07 Monocyte Monocytes Neovascularization Patrolling Cell Movement Mice Inbred NOD Sein lcsh:Science Migration Colorectal Cancer Non-classical Multidisciplinary biology Neovascularization Pathologic Extravasation medicine.anatomical_structure Cytokine Matrix Metalloproteinase 9 medicine.symptom Colorectal Neoplasms Science CD14 Breast Neoplasms GATA3 Transcription Factor Adenocarcinoma General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Interferon-gamma Cell Line Tumor medicine Animals Humans inflammation [Breast] CX3CL1 ddc:612 Inflammation business.industry Chemokine CX3CL1 Tumor Necrosis Factor-alpha General Chemistry Leukocyte 030104 developmental biology Cancer research biology.protein lcsh:Q business Neoplasm Transplantation |
Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-19 (2018) Nature Communications, Vol. 9, No 1 (2018) P. 19 Nature Communications |
ISSN: | 2041-1723 |
DOI: | 10.1038/s41467-017-02610-0 |
Popis: | 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. Circulating myeloid cells can leave the vasculature to infiltrate tumours and are thought to contribute to tumour angiogenesis. Here the authors live image monocytes that migrate to xenograft tumours and map an extravasation cascade of human proangiogenic monocytes into the tumour. |
Databáze: | OpenAIRE |
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