比利时鲁汶大学的Massimiliano Mazzone研究组发现，表达podoplanin（PDPN）的巨噬细胞能够促进乳腺癌的淋巴管生成和淋巴侵袭。该研究于2019年8月22日在线发表于《细胞—代谢》。
据悉，在乳腺肿瘤浸润性免疫细胞中，podoplanin（PDPN）最高的表达在肿瘤相关巨噬细胞（TAM）亚群中发现。
研究人员发现PDPN参与该TAM亚群与淋巴管内皮细胞（LEC）的粘附。从机制上讲，PDPN与LEC来源的半乳糖凝集素8（GAL8）以糖基化依赖性方式的结合，从而促进了迁移前整合素β1的活化。当接近淋巴管时，表达PDPN的巨噬细胞（PoEM）刺激局部基质重塑并促进血管生长和淋巴侵袭。抗整合素β1阻断、巨噬细胞特异性Pdpn敲除或GAL8都能够抑制TAM与LEC的粘附，从而抑制淋巴管生成和减少淋巴癌扩散。在乳腺癌患者中，PoEM与肿瘤淋巴管的关联与淋巴结和远处器官转移的发生率相关。
附：英文原文
Title: Podoplanin-Expressing Macrophages Promote Lymphangiogenesis and Lymphoinvasion in Breast Cancer
Author: Pawe? 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,Agnes Noel,Giuseppe Floris,Jo A. Van Ginderachter,Massimiliano Mazzone
Issue&Volume: 22 August 2019
Abstract: 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.
DOI: https://doi.org/10.1016/j.cmet.2019.07.015
Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30428-0#
Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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本期文章：《细胞—代谢》：Online/在线发表
