AI Article Synopsis
- - Tumor-associated macrophages (TAMs) play a key role in helping cancer cells spread by guiding them to blood vessels and facilitating their entry into the bloodstream.
- - The study reveals that migratory macrophages, which are actually new monocytes, transform into sessile perivascular macrophages through a process controlled by specific signaling molecules (CXCL12 and CXCR4).
- - Cancer cells increase the expression of CXCR4 in these monocytes, while fibroblasts secrete CXCL12 to attract the TAMs, ultimately supporting cancer cell movement and making blood vessels more permeable for easier cancer spread.
Article 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.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946803 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2018.04.007 | DOI Listing |
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