A Unidirectional Transition from Migratory to Perivascular Macrophage Is Required for Tumor Cell Intravasation.
Cell Rep
; 23(5): 1239-1248, 2018 05 01.
Article
em En
| MEDLINE
| ID: mdl-29719241
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-ß-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.
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Base de dados:
MEDLINE
Assunto principal:
Monócitos
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Movimento Celular
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Macrófagos
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Neoplasias Experimentais
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article