Tobias Lange, Ursula Valentiner, Daniel Wicklein, Hanna Maar, Vera Labitzky, Ann-Kristin Ahlers, Sarah Starzonek, Sandra Genduso, Lisa Staffeldt, Carolin Pahlow, Anna-Maria Dück, Christine Stürken, Anke Baranowsky, Alexander T Bauer, Etmar Bulk, Albrecht Schwab, Kristoffer Riecken, Christian Börnchen, Rainer Kiefmann, Valsamma Abraham, Horace M DeLisser, Timo Gemoll, Jens K Habermann, Andreas Block, Klaus Pantel, Udo Schumacher
Extravasation of circulating tumor cells (CTCs) is critical for metastasis and is initiated by adhesive interactions between glycoligands on CTCs and E-selectin on endothelia. Here, we show that the clinically approved proteasome inhibitor bortezomib (BZM; Velcade) counteracts the cytokine-dependent induction of E-selectin in the lung mediated by the primary tumor, thereby impairing endothelial adhesion and thus spontaneous lung metastasis in vivo. However, the efficacy of BZM crucially depends on the tumor cells' E-selectin ligands, which determine distinct adhesion patterns...
April 6, 2022: Molecular Therapy