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.
Macrophages orchestrate the expansion of a proangiogenic perivascular niche during cancer progression / Opzoomer, J. W.; Anstee, J. E.; Dean, I.; Hill, E. J.; Bouybayoune, I.; Caron, J.; Muliaditan, T.; Gordon, P.; Sosnowska, D.; Nuamah, R.; Pinder, S. E.; Ng, T.; Dazzi, F.; Kordasti, S.; Withers, D. R.; Lawrence, T.; Arnold, J. N.. - In: SCIENCE ADVANCES. - ISSN 2375-2548. - STAMPA. - 7:45(2021), p. eabg9518. [10.1126/sciadv.abg9518]
Macrophages orchestrate the expansion of a proangiogenic perivascular niche during cancer progression
Kordasti S.Writing – Review & Editing
;
2021-01-01
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
