Macrophage-induced lymphangiogenesis and metastasis following paclitaxel chemotherapy is regulated by VEGFR3

• Verfasst von: Alishekevitz, Dror [VerfasserIn]
• Verfasst von: Scherer, Sandra [VerfasserIn]
• Verfasst von: Sleeman, Jonathan P. [VerfasserIn]
• Titel: Macrophage-induced lymphangiogenesis and metastasis following paclitaxel chemotherapy is regulated by VEGFR3
• Verf.angabe: Dror Alishekevitz, Svetlana Gingis-Velitski, Orit Kaidar-Person, Lilach Gutter-Kapon, Sandra D. Scherer, Ziv Raviv, Emmanuelle Merquiol, Yael Ben-Nun, Valeria Miller, Chen Rachman-Tzemah, Michael Timaner, Yelena Mumblat, Neta Ilan, David Loven, Dov Hershkovitz, Ronit Satchi-Fainaro, Galia Blum, Jonathan P. Sleeman, Israel Vlodavsky, and Yuval Shaked
• E-Jahr: 2016
• Jahr: October 25, 2016
• Umfang: 13 S.
• Fussnoten: Gesehen am 26.06.2019
• Titel Quelle: Enthalten in: Cell reports
• Ort Quelle: Maryland Heights, MO : Cell Press, 2012
• Jahr Quelle: 2016
• Band/Heft Quelle: 17(2016), 5, Seite 1344-1356
• ISSN Quelle: 2211-1247
• DOI: doi:10.1016/j.celrep.2016.09.083
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: chemotherapy
• Sach-SW: host response
• Sach-SW: lymphangiogenesis
• Sach-SW: macrophages
• Sach-SW: metastatis
• Sach-SW: VEGF-C
• K10plus-PPN: 1667998315

Abstract

Summary - While chemotherapy strongly restricts or reverses tumor growth, the response of host tissue to therapy can counteract its anti-tumor activity by promoting tumor re-growth and/or metastases, thus limiting therapeutic efficacy. Here, we show that vascular endothelial growth factor receptor 3 (VEGFR3)-expressing macrophages infiltrating chemotherapy-treated tumors play a significant role in metastasis. They do so in part by inducing lymphangiogenesis as a result of cathepsin release, leading to VEGF-C upregulation by heparanase. We found that macrophages from chemotherapy-treated mice are sufficient to trigger lymphatic vessel activity and structure in naive tumors in a VEGFR3-dependent manner. Blocking VEGF-C/VEGFR3 axis inhibits the activity of chemotherapy-educated macrophages, leading to reduced lymphangiogenesis in treated tumors. Overall, our results suggest that disrupting the VEGF-C/VEGFR3 axis not only directly inhibits lymphangiogenesis but also blocks the pro-metastatic activity of macrophages in chemotherapy-treated mice.