Podoplanin-Expressing Macrophages Promote Lymphangiogenesis and Lymphoinvasion in Breast Cancer

被引：221

作者：

Bieniasz-Krzywiec, Pawel ^{[1
,2
,3
,4
]}

Martin-Perez, Rosa ^{[1
,2
]}

Ehling, Manuel ^{[1
,2
]}

Garcia-Caballero, Melissa ^{[5
]}

Pinioti, Sotiria ^{[1
,2
]}

Pretto, Samantha ^{[1
,2
]}

Kroes, Roel ^{[1
,2
]}

Aldeni, Chiara ^{[1
,2
]}

Di Matteo, Mario ^{[1
,2
]}

Prenen, Hans ^{[2
,6
]}

Virginia Tribulatti, Maria ^{[7
]}

Campetella, Oscar ^{[7
]}

Smeets, Ann ^{[8
]}

Noel, Agnes ^{[5
]}

Floris, Giuseppe ^{[9
]}

Van Ginderachter, Jo A. ^{[3
,4
]}

Mazzone, Massimiliano ^{[1
,2
]}

机构：

[1] VIB, Lab Tumor Inflammat & Angiogenesis, Ctr Canc Biol, B-3000 Leuven, Belgium

[2] Katholieke Univ Leuven, Dept Oncol, Lab Tumor Inflammat & Angiogenesis, Ctr Canc Biol, B-3000 Leuven, Belgium

[3] VIB Ctr Inflammat Res, Myeloid Cell Immunol Lab, B-1050 Brussels, Belgium

[4] Vrije Univ Brussel, Lab Cellular & Mol Immunol, B-1050 Brussels, Belgium

[5] Univ Liege, Lab Tumor & Dev Biol, GIGA Canc, B-4000 Liege, Belgium

[6] Univ Hosp Antwerp, Oncol Dept, B-2650 Edegem, Belgium

[7] Natl Univ San Martin, Inst Res Biotechnol, CONICET, RA-1650 Buenos Aires, DF, Argentina

[8] Katholieke Univ Leuven, Surg Oncol Unit, Dept Oncol, B-3000 Leuven, Belgium

[9] Katholieke Univ Leuven, Translat Cell & Tissue Res Unit, Dept Imaging & Pathol, B-3000 Leuven, Belgium

来源：

CELL METABOLISM | 2019年 / 30卷 / 05期

基金：

欧洲研究理事会;

关键词：

ENDOTHELIAL GROWTH-FACTOR; EPITHELIAL-MESENCHYMAL TRANSITION; MATRIX METALLOPROTEINASES; TUMOR LYMPHANGIOGENESIS; LYMPH-NODE; INTEGRIN; CELLS; ANGIOGENESIS; METASTASIS; BLOOD;

D O I：

10.1016/j.cmet.2019.07.015

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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 beta 1. When proximal to lymphatics, PDPN-expressing macrophages (PoEMs) stimulate local matrix remodeling and promote vessel growth and lymphoinvasion. Anti-integrin beta 1 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.

引用

页码：917 / 936

页数：20

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