TIE-2-expressing monocytes are lymphangiogenic and associate specifically with lymphatics of human breast cancer.

Détails

Ressource 1Télécharger: BIB_4C97ACD28497.P001.pdf (1387.90 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_4C97ACD28497
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
TIE-2-expressing monocytes are lymphangiogenic and associate specifically with lymphatics of human breast cancer.
Périodique
Oncoimmunology
Auteur(s)
Bron S., Henry L., Faes-Van't Hull E., Turrini R., Vanhecke D., Guex N., Ifticene-Treboux A., Marina Iancu E., Semilietof A., Rufer N., Lehr H.A., Xenarios I., Coukos G., Delaloye J.F., Doucey M.A.
ISSN
2162-4011 (Print)
ISSN-L
2162-4011
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
5
Numéro
2
Pages
e1073882
Langue
anglais
Résumé
In experimental mouse models of cancer, increasingly compelling evidence point toward a contribution of tumor associated macrophages (TAM) to tumor lymphangiogenesis. Corresponding experimental observations in human cancer remain scarce although lymphatic metastasis is widely recognized as a predominant route for tumor spread. We previously showed that, in malignant tumors of untreated breast cancer (BC) patients, TIE-2-expressing monocytes (TEM) are highly proangiogenic immunosuppressive cells and that TIE-2 and VEGFR signaling pathways drive TEM immunosuppressive function. We report here that, in human BC, TEM express the canonical lymphatic markers LYVE-1, Podoplanin, VEGFR-3 and PROX-1. Critically, both TEM acquisition of lymphatic markers and insertion into lymphatic vessels were observed in tumors but not in adjacent non-neoplastic tissues, suggesting that the tumor microenvironment shapes both TEM phenotype and spatial distribution. We assessed the lymphangiogenic activity of TEM isolated from dissociated primary breast tumors in vitro and in vivo using endothelial cells (EC) sprouting assay and corneal vascularization assay, respectively. We show that, in addition to their known hemangiogenic function, TEM isolated from breast tumor display a lymphangiogenic activity. Importantly, TIE-2 and VEGFR pathways display variable contributions to TEM angiogenic and lymphangiogenic activities across BC patients; however, combination of TIE-2 and VEGFR kinase inhibitors abrogated these activities and overcame inter-patient variability. These results highlight the direct contribution of tumor TEM to the breast tumor lymphatic network and suggest a combined use of TIE-2 and VEGFR kinase inhibitors as a therapeutic approach to block hem- and lymphangiogenesis in BC.
Pubmed
Web of science
Création de la notice
01/05/2016 17:00
Dernière modification de la notice
20/08/2019 14:01
Données d'usage