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Loss of Caveolin-1 in Metastasis-Associated Macrophages Drives Lung Metastatic Growth through Increased Angiogenesis.


ABSTRACT: 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).

SUBMITTER: Celus W 

PROVIDER: S-EPMC5732321 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Loss of Caveolin-1 in Metastasis-Associated Macrophages Drives Lung Metastatic Growth through Increased Angiogenesis.

Celus Ward W   Di Conza Giusy G   Oliveira Ana Isabel AI   Ehling Manuel M   Costa Bruno M BM   Wenes Mathias M   Mazzone Massimiliano M  

Cell reports 20171201 10


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 canc  ...[more]

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