Loss of Caveolin-1 in Metastasis-Associated Macrophages Drives Lung Metastatic Growth through Increased Angiogenesis
| Autor: | Ana Isabel Oliveira, Mathias Wenes, Ward Celus, Massimiliano Mazzone, Manuel Ehling, Bruno M. Costa, Giusy Di Conza |
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| Přispěvatelé: | Universidade do Minho |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Vascular Endothelial Growth Factor A
0301 basic medicine Lung Neoplasms Angiogenesis Caveolin 1 ANTICANCER THERAPIES PROGRESSION MMP9 VEGF-A Medicina Clínica [Ciências Médicas] Metastasis Mice 0302 clinical medicine Caveolin-1 CSF1 Macrophage Neoplasm Metastasis lcsh:QH301-705.5 angiogenesis macrophages metastasis VEGFR1 Animals Macrophages Mice Knockout Neovascularization Pathologic Signal Transduction Vascular Endothelial Growth Factor Receptor-2 MONOCYTE CHEMOATTRACTANT PROTEIN-1 Primary tumor 3. Good health TUMOR-ASSOCIATED MACROPHAGES Vascular endothelial growth factor A 030220 oncology & carcinogenesis Life Sciences & Biomedicine EXPRESSION Knockout Biology Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences MICROVASCULAR PERMEABILITY medicine BREAST-CANCER Neovascularization Ciências Médicas::Medicina Clínica Pathologic Science & Technology RECEPTOR Cancer Cell Biology medicine.disease MICE 030104 developmental biology lcsh:Biology (General) CELLS Cancer research |
| Zdroj: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP Cell Reports, Vol 21, Iss 10, Pp 2842-2854 (2017) Cell Reports |
| Popis: | Summary Although it is well established that tumor-associated macrophages take part in each step of cancer progression, less is known about the distinct role of the so-called metastasis-associated macrophages (MAMs) at the metastatic site. Previous studies reported that Caveolin-1 (Cav1) has both tumor-promoting and tumor-suppressive functions. However, the role of Cav1 in bone-marrow-derived cells is unknown. Here, we describe Cav1 as an anti-metastatic regulator in mouse models of lung and breast cancer pulmonary metastasis. Among all the recruited inflammatory cell populations, we show that MAMs uniquely express abundant levels of Cav1. Using clodronate depletion of macrophages, we demonstrate that macrophage Cav1 signaling is critical for metastasis and not for primary tumor growth. In particular, Cav1 inhibition does not affect MAM recruitment to the metastatic site but, in turn, favors angiogenesis. We describe a mechanism by which Cav1 in MAMs specifically restrains vascular endothelial growth factor A/vascular endothelial growth factor receptor 1 (VEGF-A/VEGFR1) signaling and its downstream effectors, matrix metallopeptidase 9 (MMP9) and colony-stimulating factor 1 (CSF1). Graphical Abstract Highlights • Macrophage Cav1 signaling is critical for restraining lung metastatic growth • Cav1 deletion in macrophages favors angiogenesis at the lung metastatic site • Cav1 suppresses VEGF-A/VEGFR1 activity and its downstream effectors, MMP9 and CSF1 Celus et al. show an intrinsic anti-metastatic surveillance mechanism in the lung microenvironment whereby upregulation of Caveolin-1 in metastasis-associated macrophages specifically controls the excessive exposure of VEGFR1 at the cell surface and thereby limits downstream MMP9 and CSF1 expression, angiogenesis, and metastatic growth. |
| Databáze: | OpenAIRE |
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