A Unidirectional Transition from Migratory to Perivascular Macrophage Is Required for Tumor Cell Intravasation.
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Embargo End Date
ICR Authors
Authors
Arwert, EN
Harney, AS
Entenberg, D
Wang, Y
Sahai, E
Pollard, JW
Condeelis, JS
Harney, AS
Entenberg, D
Wang, Y
Sahai, E
Pollard, JW
Condeelis, JS
Document Type
Journal Article
Date
2018-05-01
Date Accepted
2018-03-30
Abstract
Tumor-associated macrophages (TAMs) are critical for tumor metastasis. Two TAM subsets support cancer cell intravasation: migratory macrophages guide cancer cells toward blood vessels, where sessile perivascular macrophages assist their entry into the blood. However, little is known about the inter-relationship between these functionally distinct TAMs or their possible inter-conversion. We show that motile, streaming TAMs are newly arrived monocytes, recruited via CCR2 signaling, that then differentiate into the sessile perivascular macrophages. This unidirectional process is regulated by CXCL12 and CXCR4. Cancer cells induce TGF-β-dependent upregulation of CXCR4 in monocytes, while CXCL12 expressed by perivascular fibroblasts attracts these motile TAMs toward the blood vessels, bringing motile cancer cells with them. Once on the blood vessel, the migratory TAMs differentiate into perivascular macrophages, promoting vascular leakiness and intravasation.
Citation
Cell reports, 2018, 23 (5), pp. 1239 - 1248
Source Title
Cell reports
Publisher
CELL PRESS
ISSN
2211-1247
eISSN
2211-1247
Collections
Research Team
Functional Tumour Immunol