Adiponectin promotes VEGF-A-dependent angiogenesis in human chondrosarcoma through PI3K, Akt, mTOR, and HIF-α pathway
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// Hsiang-Ping Lee 1, 2, * , Chih-Yang Lin 3, * , Jhao-Sheng Shih 3 , Yi-Chin Fong 4, 5 , Shih-Wei Wang 6 , Te-Mao Li 7 , Chih-Hsin Tang 3, 8, 9 1 Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan 2 Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan 3 Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan 4 Department of Sports Medicine, China Medical University, Taichung, Taiwan 5 Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan 6 Department of Medicine, Mackay Medical College, New Taipei City, Taiwan 7 School of Chinese Medicine, China Medical University, Taichung, Taiwan 8 Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan 9 Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan * These authors have contributed equally to this work Correspondence to: Chih-Hsin Tang, e-mail: chtang@mail.cmu.edu.tw Te-Mao Li, e-mail: leedemaw@mail.cmu.edu.tw Keywords: adiponectin, chondrosarcoma, angiogenesis, VEGF-A, HIF Received: May 05, 2015 Accepted: October 02, 2015 Published: October 12, 2015 ABSTRACT Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes. On the other hand, angiogenesis is a critical step in tumor growth and metastasis. However, the relationship of adiponectin with vascular endothelial growth factor-A (VEGF-A) expression and angiogenesis in human chondrosarcoma is mostly unknown. In this study we first demonstrated that the expression of adiponectin was correlated with tumor stage of human chondrosarcoma tissues. In addition, we also found that adiponectin increased VEGF-A expression in human chondrosarcoma cells and subsequently induced migration and tube formation in human endothelial progenitor cells (EPCs). Adiponectin promoted VEGF-A expression through adiponectin receptor (AdipoR), phosphoinositide 3 kinase (PI3K), Akt, mammalian target of rapamycin (mTOR), and hypoxia-inducible factor-1α (HIF)-1α signaling cascades. Knockdown of adiponectin decreased VEGF-A expression and also abolished chondrosarcoma conditional medium-mediated tube formation in EPCs in vitro as well as angiogenesis effects in the chick chorioallantoic membrane and Matrigel plug nude mice model in vivo . Therefore, adiponectin is crucial for tumor angiogenesis and growth, which may represent a novel target for anti-angiogenic therapy in human chondrosarcoma.
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Adipose tissue secretes several adipokines and endogenous angiogenesis inhibitors that modulate new blood vessel formation, including adiponectin, leptin, resistin, visfatin/thrombospondin 1, and plasminogen activator inhibitor.
“In addition to authentic angiogenic factors, AT secretes several important adipokines and endogenous angiogenesis inhibitors to modulate the balance of new blood vessel formation, including adiponectin (36,37), leptin (34), resistin (38), visfatin/thrombospondin 1 (39), and plasminogen activator inhibitor (40).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [36]
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“Finally, Acrp30, through the suppression of NF-kB phosphorylation, suppresses the pro-inflammatory and anti-apoptotic related properties [16,30].”
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“Our recent study demonstrated that adiponectin promoted angiogenesis in human chondrosarcomas through adiponectin receptors and the PI3K/Akt/mTOR/HIF signaling pathway [34].”
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“VEGF-A expression was induced by adiponectin through the utilization of the adiponectin receptor, PI3K, AKT, mTOR and HIF-1a pathways 7,59.”
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“In human chondrosarcoma cells, VEGF-A expression and angiogenesis are increased owing to phosphoinositide 3-kinase (PI3K), Akt, mammalian target of rapamycin (mTOR), and hypoxiainducible factor-1alpha (HIF-1-alpha signaling cascades (Lee et al. 2015).”
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“Angiogenesis is promoted by VEGF, but HIF-1 α is not the only factor that stimulates VEGF expression in chondrosarcomas [121].”
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“…have been shown to correlate with the tumor stage of human ChSs. Lee HP and coworkers demonstrated that adiponectin induces ChS cells to secrete VEGF-A that, in turn, triggers migration and tube formation of human endothelial progenitor cells through PI3K, Akt, mTOR, and HIF-1alpha pathways [69].”
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“In another study, protein hormone adiponectin promoted VEGF-A expression in human chondrosarcoma cell lines via PI3k, Akt, mTOR, and hypoxia-inducible factor-1a signaling cascades (12).”
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“Consistent with our study, adiponectin promotes VEGF-A expression via multiple mechanisms, including adiponectin receptor (AdipoR), Akt, mammalian target of rapamycin (mTOR), PI3K, and HIF-1a signaling pathways in human chondrosarcoma cells (Lee et al. 2015).”
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“The above genes were chosen for analysis due to their recognized importance in the chondrosarcoma pathology and biology reports of others [15, 28, 32, 34].”
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“Furthermore, APN promoted VEGF-A expression through the phosphoinositide 3 kinase (PI3K)/Akt and mTOR signaling pathways in human chondrosarcoma (Lee et al. 2015).”
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“In certain diseases such as chondrosarcoma [52] and rheumatoid arthritis [53], adiponectin promotes VEGFA-dependent angiogenesis.”
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- Authors
- Lee, H.-P., Lin, C.-Y., Shih, J.-S., Fong, Y.-C., Wang, S.-W., Li, T.-M., & Tang, C.-H.
- Affiliations
- China Medical University (TW)
- Mackay Medical University (TW)
- Asia University (TW)
- Corresponding author
- Lee, Hsiang-Ping
- Lin, Chih-Yang
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2015-10-12
- Volume
- 6
- Issue
- 34
- Pages
- 36746-36761
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC4742208
- OpenAlex
- W2231721040
- Cited by
- 94
- References
- 49
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 10 · 2023: 6 · 2022: 7 · 2021: 12 · 2020: 7 · 2019: 9 · 2018: 11 · 2017: 7 · 2016: 9 · 2015: 1 · 2014: 1
- FWCI
- 7.84
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Ministry of Science and Technology, Taiwan
- Topics
- Health Sciences › Medicine › Rheumatology › Bone Tumor Diagnosis and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Keywords
- adiponectin, chondrosarcoma, angiogenesis, VEGF-A, PI3K/AKT/mTOR pathway, endothelial progenitor cells, tumor stage, metastasis, tumor growth, tumor microenvironment, tumor hypoxia, tube formation, tumor vasculature, adipokines
- MeSH terms
- Animals, Bone Neoplasms, Chick Embryo, Chondrosarcoma, Humans, Male, Mice, Inbred BALB C, Mice, Nude, Neovascularization, Pathologic, Transfection, Mice, SCID, Phosphatidylinositol 3-Kinases, Vascular Endothelial Growth Factor A, Proto-Oncogene Proteins c-akt, Mice, Hypoxia-Inducible Factor 1, alpha Subunit, Adiponectin, TOR Serine-Threonine Kinases, Heterografts
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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