Details

Autor(en) / Beteiligte

• Noh, Kyunghee
• Mangala, Lingegowda S.
• Han, Hee-Dong
• Zhang, Ningyan
• Pradeep, Sunila
• Wu, Sherry Y.
• Ma, Shaolin
• Mora, Edna
• Rupaimoole, Rajesha
• Jiang, Dahai
• Wen, Yunfei
• Shahzad, Mian M.K.
• Lyons, Yasmin
• Cho, MinSoon
• Hu, Wei
• Nagaraja, Archana S.
• Haemmerle, Monika
• Mak, Celia S.L.
• Chen, Xiuhui
• Gharpure, Kshipra M.
• Deng, Hui
• Xiong, Wei
• Kingsley, Charles V.
• Liu, Jinsong
• Jennings, Nicholas
• Birrer, Michael J.
• Bouchard, Richard R.
• Lopez-Berestein, Gabriel
• Coleman, Robert L.
• An, Zhiqiang
• Sood, Anil K.

Titel

Differential Effects of EGFL6 on Tumor versus Wound Angiogenesis

Ist Teil von

• Cell reports (Cambridge), 2017-12, Vol.21 (10), p.2785-2795

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Angiogenesis inhibitors are important for cancer therapy, but clinically approved anti-angiogenic agents have shown only modest efficacy and can compromise wound healing. This necessitates the development of novel anti-angiogenesis therapies. Here, we show significantly increased EGFL6 expression in tumor versus wound or normal endothelial cells. Using a series of in vitro and in vivo studies with orthotopic and genetically engineered mouse models, we demonstrate the mechanisms by which EGFL6 stimulates tumor angiogenesis. In contrast to its antagonistic effects on tumor angiogenesis, EGFL6 blockage did not affect normal wound healing. These findings have significant implications for development of anti-angiogenesis therapies. [Display omitted] •High EGFL6 expression in the tumor vasculature was related to poor overall survival•TWIST1 regulates EGFL6 transcriptional activity and can promote angiogenesis•EGFL6 regulates PI3K/AKT signaling via integrin-Tie2 crosstalk•EGFL6 antibodies effectively block tumor angiogenesis without affecting healing wounds Noh et al. identify EGFL6 as an angiogenic target that is selectively present in tumor endothelial cells in a hypoxic tumor microenvironment. EGFL6 blockade exerts robust anti-angiogenic and anti-tumor effects without affecting wound healing. These findings suggest an important approach for effectively targeting tumor angiogenesis.