Cell Reports (Dec 2017)
Differential Effects of EGFL6 on Tumor versus Wound Angiogenesis
- Kyunghee Noh,
- Lingegowda S. Mangala,
- Hee-Dong Han,
- Ningyan Zhang,
- Sunila Pradeep,
- Sherry Y. Wu,
- Shaolin Ma,
- Edna Mora,
- Rajesha Rupaimoole,
- Dahai Jiang,
- Yunfei Wen,
- Mian M.K. Shahzad,
- Yasmin Lyons,
- MinSoon Cho,
- Wei Hu,
- Archana S. Nagaraja,
- Monika Haemmerle,
- Celia S.L. Mak,
- Xiuhui Chen,
- Kshipra M. Gharpure,
- Hui Deng,
- Wei Xiong,
- Charles V. Kingsley,
- Jinsong Liu,
- Nicholas Jennings,
- Michael J. Birrer,
- Richard R. Bouchard,
- Gabriel Lopez-Berestein,
- Robert L. Coleman,
- Zhiqiang An,
- Anil K. Sood
Affiliations
- Kyunghee Noh
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Gene Therapy Research Unit, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
- Lingegowda S. Mangala
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Hee-Dong Han
- Department of Immunology, School of Medicine, Konkuk University, Chungju 380-701, South Korea
- Ningyan Zhang
- Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
- Sunila Pradeep
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
- Sherry Y. Wu
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Shaolin Ma
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Edna Mora
- Department of Surgery, University of Puerto Rico, San Juan 00936, Puerto Rico; University of Puerto Rico Comprehensive Cancer Center, San Juan 00936, Puerto Rico; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77584, USA
- Rajesha Rupaimoole
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Dahai Jiang
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Yunfei Wen
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Mian M.K. Shahzad
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Yasmin Lyons
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- MinSoon Cho
- Department of Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Wei Hu
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Archana S. Nagaraja
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Monika Haemmerle
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Celia S.L. Mak
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Xiuhui Chen
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Kshipra M. Gharpure
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Hui Deng
- Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
- Wei Xiong
- Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
- Charles V. Kingsley
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Jinsong Liu
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Nicholas Jennings
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Michael J. Birrer
- University of Alabama Comprehensive Cancer Center, Birmingham, AL 35294, USA
- Richard R. Bouchard
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Gabriel Lopez-Berestein
- Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Robert L. Coleman
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Zhiqiang An
- Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
- Anil K. Sood
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Corresponding author
- Journal volume & issue
-
Vol. 21,
no. 10
pp. 2785 – 2795
Abstract
Summary: 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. : 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. Keywords: tumor endothelial cells, ovarian cancer, chitosan nanoparticles, tumor vasculature, wound healing
