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

Publié dans: Sci Adv 2021 Nov; 7(45): eabg9518

Auteurs: Opzoomer JW, Anstee JE, Dean I, Hill EJ, Bouybayoune I, Caron J, Muliaditan T, Gordon P, Sosnowska D, Nuamah R, Pinder SE, Ng T, Dazzi F, Kordasti S, Withers DR, Lawrence T, Arnold JN

Résumé

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 α-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.

Lien vers Pubmed [PMID] – 34730997

Lien vers HAL – amu-03566003

Lien vers le DOI – 10.1126/sciadv.abg9518