Podoplanin-Expressing Macrophages Promote Lymphangiogenesis and Lymphoinvasion in Breast Cancer.,Cell Metabolism

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Podoplanin-Expressing Macrophages Promote Lymphangiogenesis and Lymphoinvasion in Breast Cancer.
Cell Metabolism ( IF 27.7 ) Pub Date : 2019-08-22 , DOI: 10.1016/j.cmet.2019.07.015
Paweł Bieniasz-Krzywiec ₁ , Rosa Martín-Pérez ₂ , Manuel Ehling ₂ , Melissa García-Caballero ₃ , Sotiria Pinioti ₂ , Samantha Pretto ₂ , Roel Kroes ₂ , Chiara Aldeni ₂ , Mario Di Matteo ₂ , Hans Prenen ₄ , María Virginia Tribulatti ₅ , Oscar Campetella ₅ , Ann Smeets ₆ , Agnes Noel ₃ , Giuseppe Floris ₇ , Jo A Van Ginderachter ₈ , Massimiliano Mazzone ₂

Affiliation

Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven B3000, Belgium; Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven B3000, Belgium; Myeloid Cell Immunology Laboratory, VIB Center for Inflammation Research, Brussels B1050, Belgium; Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels B1050, Belgium.
Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven B3000, Belgium; Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven B3000, Belgium.
Laboratory of Tumor and Developmental Biology, GIGA-Cancer, University of Liège, Sart-Tilman, B4000 Liège, Belgium.
Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven B3000, Belgium; Oncology Department, University Hospital Antwerp, 2650 Edegem, Belgium.
Institute for Research in Biotechnology, National University of San Martín, CONICET, Buenos Aires 1650, Argentina.
Surgical Oncology Unit, Department of Oncology, KU Leuven, Leuven B3000, Belgium.
Translational Cell and Tissue Research Unit, Department of Imaging and Pathology, KU Leuven, Leuven B3000, Belgium.
Myeloid Cell Immunology Laboratory, VIB Center for Inflammation Research, Brussels B1050, Belgium; Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels B1050, Belgium.

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.

中文翻译：

表达 Podoplanin 的巨噬细胞促进乳腺癌中的淋巴管生成和淋巴浸润。

在乳腺肿瘤浸润免疫细胞中，在肿瘤相关巨噬细胞 (TAM) 的一个子集中发现了最高表达的 podoplanin (PDPN)。我们在此证明 PDPN 参与了该 TAM 子集与淋巴管内皮细胞 (LEC) 的附着。从机制上讲，PDPN 与 LEC 衍生的半乳糖凝集素 8 (GAL8) 以糖基化依赖性方式的结合促进了促迁移整合素 β1 的激活。当靠近淋巴管时，表达 PDPN 的巨噬细胞 (PoEM) 会刺激局部基质重塑并促进血管生长和淋巴浸润。抗整合素 β1 阻断、巨噬细胞特异性 Pdpn 敲除或 GAL8 抑制会削弱 TAM 与 LEC 的粘附，抑制淋巴管生成并减少淋巴癌扩散。在乳腺癌患者中，

更新日期：2019-11-09

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