Journal article
Obesity-associated inflammation promotes angiogenesis and breast cancer via angiopoietin-like 4
Oncogene, Vol.38(13), pp.2351-2363
03/2019
DOI: 10.1038/s41388-018-0592-6
PMCID: PMC6440811
PMID: 30518876
Abstract
Obesity is a risk factor for breast cancer and also predicts poor clinical outcomes regardless of menopausal status. Contributing to the poor clinical outcomes is the suboptimal efficacy of standard therapies due to dose limiting toxicities and obesity-related complications, highlighting the need to develop novel therapeutic approaches for treating obese patients. We recently found that obesity leads to an increase in tumor-infiltrating macrophages with activated NLRC4 inflammasome and increased interleukin (IL)-1β production. IL-1β, in turn, leads to increased angiogenesis and cancer progression. Using Next Generation RNA sequencing, we identified an NLRC4/IL-1β-dependent upregulation of angiopoietin-like 4 (ANGPTL4), a known angiogenic factor in cancer, in tumors from obese mice. ANGPTL4-deficiency by genetic knockout or treatment with a neutralizing antibody led to a significant reduction in obesity-induced angiogenesis and tumor growth. At a mechanistic level, ANGPTL4 expression is induced by IL-1β from primary adipocytes in a manner dependent on NF-κB- and MAP kinase-activation, which is further enhanced by hypoxia. This report shows that adipocyte-derived ANGPTL4 drives disease progression under obese conditions and is a potential therapeutic target for treating obese breast cancer patients.
Details
- Title: Subtitle
- Obesity-associated inflammation promotes angiogenesis and breast cancer via angiopoietin-like 4
- Creators
- Ryan Kolb - Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, 32610, USA. ryankolb@ufl.eduPaige Kluz - Free Radical and Radiation Biology, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USAZhen Wei Tan - School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, USANicholas Borcherding - Cancer Biology Graduate Program, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USANicholas Bormann - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USAAjaykumar Vishwakarma - Cancer Biology Graduate Program, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USALouis Balcziak - Interdisciplinary Neuroscience graduate program, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USAPengcheng Zhu - School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, USABrandon Sj Davies - Department of Biochemistry, Fraternal Order of Eagles Diabetes Research Center, and Obesity Research and Education Initiative, University of Iowa, Iowa City, IA, 52242, USAFrancoise Gourronc - Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USALing-Zhi Liu - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USAXin Ge - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USABing-Hua Jiang - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USAKatherine Gibson-Corley - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USAAloysius Klingelhutz - Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USANguan Soon Tan - KK Research Centre, KK Women's and Children Hospital, 100 Bukit Timah Road, Singapore, 229899, SingaporeYuwen Zhu - Department of Surgery, University of Colorado, Denver/Anschutz Medical Campus, Aurora, CO, 80045, USAFayyaz S Sutterwala - Department of Medicine, Cedars- Sinai Medical Center, Los Angeles, CA, 90048, USAXian Shen - Division of Gastrointestinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325035, China. shenxian1120@126.comWeizhou Zhang - Cancer Biology Graduate Program, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA. zhangw@ufl.edu
- Resource Type
- Journal article
- Publication Details
- Oncogene, Vol.38(13), pp.2351-2363
- Publisher
- England
- DOI
- 10.1038/s41388-018-0592-6
- PMID
- 30518876
- PMCID
- PMC6440811
- ISSN
- 1476-5594
- eISSN
- 1476-5594
- Grant note
- P30 ES005605 / NIEHS NIH HHS T32 AI007260 / NIAID NIH HHS T32 AI007260 / Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID) T32 GM007337 / NIGMS NIH HHS R01 CA193511 / NCI NIH HHS F30 CA206255 / NCI NIH HHS P30 CA086862 / NCI NIH HHS MOE2014-T2-1-012 / Ministry of Education - Singapore (MOE) R01HL130146 / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01 CA203834 / NCI NIH HHS R01 HL130146 / NHLBI NIH HHS F30 CA206255 / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01 AI118719 / NIAID NIH HHS R01AI118719 / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01 AI104706 / NIAID NIH HHS R01 CA200673 / NCI NIH HHS CA203834 / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA200673 / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA086862 / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
- Language
- English
- Date published
- 03/2019
- Academic Unit
- Dermatology; Microbiology and Immunology; Pathology; Orthopedics and Rehabilitation; Radiation Oncology; Biochemistry and Molecular Biology; Ophthalmology and Visual Sciences
- Record Identifier
- 9984003044702771
Metrics
17 Record Views