Macrophages orchestrate the expansion of a pro-angiogenic 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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Tumor associated macrophages (TAMs) are a highly plastic stromal cell type which 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) which 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 which express alpha-smooth muscle actin and phenotypically resemble pericytes. Using photolabeling techniques 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 pro-angiogenic niche. This study highlights the inter-reliance of the immune and non-immune stromal network which support cancer progression and provides therapeutic opportunities for tackling the disease.
Original languageEnglish
JournalScience Advances
Publication statusPublished - 3 Nov 2021

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