A Unidirectional Transition from Migratory to Perivascular Macrophage Is Required for Tumor Cell Intravasation

Esther N. Arwert, Allison S. Harney, David R. Entenberg, Yarong Wang, Erik Sahai, Jeffrey W. Pollard, John S. Condeelis

Research output: Contribution to journalArticle

16 Citations (Scopus)

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. Tumor-associated macrophages (TAMs) are essential for metastasis. Arwert et al. show that, following extravasation, monocytes initially become motile TAMs. Tumor-derived TGF-β then induces CXCR4 on TAMs, stimulating them to migrate toward CXCL12-expressing perivascular fibroblasts. Once adjacent to blood vessels, TAMs differentiate into metastasis-assisting perivascular TAMs.

Original languageEnglish (US)
Pages (from-to)1239-1248
Number of pages10
JournalCell Reports
Volume23
Issue number5
DOIs
StatePublished - May 1 2018

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Macrophages
Tumors
Cells
Neoplasms
Blood vessels
Vascular Tissue Neoplasms
Blood Vessels
Monocytes
Fibroblasts
Neoplasm Metastasis

Keywords

  • breast cancer
  • CCR2
  • CXCR4
  • Mena
  • metastasis
  • TAMs
  • TGF beta
  • TMEM
  • tumor associated macrophages

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

A Unidirectional Transition from Migratory to Perivascular Macrophage Is Required for Tumor Cell Intravasation. / Arwert, Esther N.; Harney, Allison S.; Entenberg, David R.; Wang, Yarong; Sahai, Erik; Pollard, Jeffrey W.; Condeelis, John S.

In: Cell Reports, Vol. 23, No. 5, 01.05.2018, p. 1239-1248.

Research output: Contribution to journalArticle

Arwert, Esther N. ; Harney, Allison S. ; Entenberg, David R. ; Wang, Yarong ; Sahai, Erik ; Pollard, Jeffrey W. ; Condeelis, John S. / A Unidirectional Transition from Migratory to Perivascular Macrophage Is Required for Tumor Cell Intravasation. In: Cell Reports. 2018 ; Vol. 23, No. 5. pp. 1239-1248.
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