Research output: Contribution to journal › Article › peer-review
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
Original language | English |
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Article number | eabg9518 |
Pages (from-to) | eabg9518 |
Journal | Science Advances |
Volume | 7 |
Issue number | 45 |
Early online date | 3 Nov 2021 |
DOIs | |
E-pub ahead of print | 3 Nov 2021 |
Published | 5 Nov 2021 |
Additional links |
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.
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