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

[en] 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 beta1. When proximal to lymphatics, PDPN-expressing macrophages (PoEMs) stimulate local matrix remodeling and promote vessel growth and lymphoinvasion. Anti-integrin beta1 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.

Disciplines :

Oncology

Author, co-author :

Bieniasz-Krzywiec, Pawel

Martin-Perez, Rosa

Ehling, Manuel

Garcia-Caballero, Melissa

Pinioti, Sotiria

Pretto, Samantha

Kroes, Roel

Aldeni, Chiara

Di Matteo, Mario

Prenen, Hans

More authors (7 more)

Language :

English

Title :

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

Publication date :

2019

Journal title :

Cell Metabolism

ISSN :

1550-4131

eISSN :

1932-7420

Publisher :

Cell Press, United States

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Available on ORBi :

since 03 September 2019

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