| Literature DB >> 31447322 |
Paweł Bieniasz-Krzywiec1, Rosa Martín-Pérez2, Manuel Ehling2, Melissa García-Caballero3, Sotiria Pinioti2, Samantha Pretto2, Roel Kroes2, Chiara Aldeni2, Mario Di Matteo2, Hans Prenen4, María Virginia Tribulatti5, Oscar Campetella5, Ann Smeets6, Agnes Noel3, Giuseppe Floris7, Jo A Van Ginderachter8, Massimiliano Mazzone9.
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.Entities:
Keywords: breast cancer; lymph nodes; lymphangiogenesis; lymphoinvasion; metastasis; podoplanin; tumor-associated macrophages
Mesh：
Substances：
Year: 2019 PMID： 31447322 DOI： 10.1016/j.cmet.2019.07.015
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287