期刊
CELL REPORTS
卷 17, 期 5, 页码 1344-1356出版社
CELL PRESS
DOI: 10.1016/j.celrep.2016.09.083
关键词
-
类别
资金
- European Research Council [260633]
- Israel Science Foundation [490/12]
- Israel Cancer Research Funds [708/12]
- German Israel Foundation [1204-253.13/2012]
- Israeli Society for Clinical Oncology and Radiation Therapy
- European Research Council (ERC) [260633] Funding Source: European Research Council (ERC)
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据