Macrophages orchestrate the expansion of a proangiogenic perivascular niche during cancer progression

James W Opzoomer, Joanne E Anstee, Isaac Dean, Emily J Hill, Ihssane Bouybayoune, Jonathan Caron, Tamara Muliaditan, Peter Gordon, Dominika Sosnowska, Rosamond Nuamah, Sarah E Pinder, Tony Ng, Francesco Dazzi, Shahram Kordasti, David R Withers, Toby Lawrence, James N Arnold

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Tumor-associated macrophages (TAMs) are a highly plastic stromal cell type that support cancer progression. Using single-cell RNA sequencing of TAMs from a spontaneous murine model of mammary adenocarcinoma (MMTV-PyMT), we characterize a subset of these cells expressing lymphatic vessel endothelial hyaluronic acid receptor 1 (Lyve-1) that spatially reside proximal to blood vasculature. We demonstrate that Lyve-1 + TAMs support tumor growth and identify a pivotal role for these cells in maintaining a population of perivascular mesenchymal cells that express -smooth muscle actin and phenotypically resemble pericytes. Using photolabeling techniques, we show that mesenchymal cells maintain their prevalence in the growing tumor through proliferation and uncover a role for Lyve-1 + TAMs in orchestrating a selective platelet-derived growth factor–CC–dependent expansion of the perivascular mesenchymal population, creating a proangiogenic niche. This study highlights the inter-reliance of the immune and nonimmune stromal network that supports cancer progression and provides therapeutic opportunities for tackling the disease.

Original languageEnglish
Article numbereabg9518
Pages (from-to)eabg9518
JournalScience Advances
Volume7
Issue number45
Early online date3 Nov 2021
DOIs
Publication statusPublished - 5 Nov 2021

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