Proangiogenic Contribution of Adiponectin toward Mammary Tumor Growth In vivo
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Abstract
Purpose: Adipocytes represent one of the most abundant constituents of the mammary gland. They are essential for mammary tumor growth and survival. Metabolically, one of the more important fat-derived factors (“adipokines”) is adiponectin (APN). Serum concentrations of APN negatively correlate with body mass index and insulin resistance. To explore the association of APN with breast cancer and tumor angiogenesis, we took an in vivo approach aiming to study its role in the mouse mammary tumor virus (MMTV)-polyoma middle T antigen (PyMT) mammary tumor model. Experimental Design: We compared the rates of tumor growth in MMTV-PyMT mice in wild-type and APN-null backgrounds. Results: Histology and micro-positron emission tomography imaging show that the rate of tumor growth is significantly reduced in the absence of APN at early stages. PyMT/APN knockout mice exhibit a reduction in their angiogenic profile resulting in nutrient deprivation of the tumors and tumor-associated cell death. Surprisingly, in more advanced malignant stages of the disease, tumor growth develops more aggressively in mice lacking APN, giving rise to a larger tumor burden, an increase in the mobilization of circulating endothelial progenitor cells, and a gene expression fingerprint indicative of more aggressive tumor cells. Conclusions: These observations highlight a novel important contribution of APN in mammary tumor development and angiogenesis, indicating that APN has potent angio-mimetic properties in tumor vascularization. However, in tumors deprived of APN, this antiangiogenic stress results in an adaptive response that fuels tumor growth through mobilization of circulating endothelial progenitor cells and the development of mechanisms enabling massive cell proliferation despite a chronically hypoxic microenvironment.
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Adiponectin has potent angiomimetic properties in tumor vascularization.
“Using a genetic approach, our laboratory identified that adiponectin has potent angiomimetic properties in tumor vascularization (75).”
From Adipose tissue remodeling and obesity (2011) · cites this paper as [75]
Adiponectin has been shown to induce angiogenesis in hypoxic fat pads and tumors.
“Adiponectin, for example, has been shown to induce angiogenesis in hypoxic fat pads and tumors (75,91)”
From Adipose tissue remodeling and obesity (2011) · cites this paper as [75]
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- Authors
- Landskroner-Eiger, S., Qian, B., Muise, E. S., Nawrocki, A. R., Berger, J. P., Fine, E. J., Koba, W., Deng, Y., Pollard, J. W., & Scherer, P. E.
- Affiliations
- 1Cell Biology, Departments of
- 2Developmental and Molecular Biology, Center of Reproductive Biology and Womens' Health, Albert Einstein Cancer Center, and
- 4Molecular Profiling and
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Albert Einstein College of Medicine (US)
- The University of Texas Southwestern Medical Center (US)
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2009-05-15
- Volume
- 15
- Issue
- 10
- Pages
- 3265-3276
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC3237387
- OpenAlex
- W2118763988
- Cited by
- 145
- References
- 51
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 5 · 2020: 7 · 2019: 7 · 2018: 5 · 2017: 12 · 2016: 7 · 2015: 10 · 2014: 10 · 2013: 23 · 2012: 15
- FWCI
- 6.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- National Cancer Institute (R01CA112023)
- National Institute of General Medical Sciences (T32-GM04791)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- adiponectin, mammary tumor growth, tumor angiogenesis, breast cancer, adipokines, MMTV-PyMT mice, endothelial progenitor cells, tumor hypoxia, tumor microenvironment, tumor vascularization
- MeSH terms
- Animals, Antigens, Viral, Tumor, Female, Flow Cytometry, Glucose, Male, Mammary Tumor Virus, Mouse, Mammary Neoplasms, Experimental, Mice, Inbred C57BL, Neovascularization, Pathologic, Polyomavirus, Time Factors, Blotting, Western, Gene Expression Regulation, Neoplastic, Apoptosis, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Vascular Endothelial Growth Factor A, Thiazolidinediones, Tumor Burden, PPAR gamma, Positron-Emission Tomography, Mice, Adiponectin
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