平足蛋白
淋巴管新生
淋巴系统
淋巴管
淋巴管内皮
癌症研究
整合素
巨噬细胞
医学
肿瘤微环境
转移
免疫系统
癌症
生物
病理
免疫学
受体
内科学
体外
生物化学
作者
Paweł Bieniasz-Krzywiec,Rosa Martín‐Pérez,Manuel Ehling,Melissa García‐Caballero,Sotiria Pinioti,Samantha Pretto,Roel Kroes,Chiara Aldeni,Mario Di Matteo,Hans Prenen,María Virginia Tribulatti,Oscar Campetella,Ann Smeets,Agnès Noël,Giuseppe Floris,Jo A. Van Ginderachter,Massimiliano Mazzone
出处
期刊:Cell Metabolism
[Elsevier]
日期:2019-11-01
卷期号:30 (5): 917-936.e10
被引量:164
标识
DOI:10.1016/j.cmet.2019.07.015
摘要
Summary
Among mammary tumor-infiltrating immune cells, the highest expression of podoplanin (PDPN) is found in a subset of tumor-associated macrophages (TAMs). We hereby demonstrate that PDPN is involved in the attachment of this TAM subset to lymphatic endothelial cells (LECs). Mechanistically, the binding of PDPN to LEC-derived galectin 8 (GAL8) in a glycosylation-dependent manner promotes the activation of pro-migratory integrin β1. When proximal to lymphatics, PDPN-expressing macrophages (PoEMs) stimulate local matrix remodeling and promote vessel growth and lymphoinvasion. Anti-integrin β1 blockade, macrophage-specific Pdpn knockout, or GAL8 inhibition impairs TAM adhesion to LECs, restraining lymphangiogenesis and reducing lymphatic cancer spread. In breast cancer patients, association of PoEMs with tumor lymphatic vessels correlates with incidences of lymph node and distant organ metastasis.
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