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Cited by 137Peroxisome Proliferator-Activated ReceptorsAngiogenesis and VEGF in CancerCancer, Lipids, and Metabolism

PPARγ as a therapeutic target for tumor angiogenesis and metastasis

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Panigraphy, Danik, Huang, Sui, Kieran, Mark W., Kaipainen, Arja·2005·Cancer Biology & Therapy
DOI 10.4161/cbt.4.7.2014
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Abstract

Peroxisome proliferator activated receptors (PPARs) are ligand-activated transcription factors with pleiotropic effects on cell fate and metabolism. Because of its anti-proliferative, pro-apoptotic and differentiation promoting activities, PPARgamma has been intensively evaluated as a target for anti-cancer therapy in preclinical models. However, PPARgamma has been reported to act both as a promoter and suppressor of neoplasia, and the role of PPARgamma activating ligands as well as antagonists in therapy remains controversial. In the past decade a new picture of tumors as a disease that involves changes in the non-cancerous tumor bed, including angiogenesis, inflammation and other stromal changes has emerged. PPARgamma has strong anti-inflammatory and anti-angiogenic effects, extending the repertoire of potential targets of PPARgamma ligands beyond cell autonomous mechanisms of cancer. The heterogeneous cellular targets and the biphasic effects of PPARgamma on various pro and anti-tumor processes may account for the apparent paradoxical effects of PPARgamma agonists. Here we review the action of PPARgamma agonists on angiogenesis and inflammation in the context of tumorigenesis as an integrated tissue process and discuss potential explanations for the conflicting effects of PPARgamma agonists on tumor progression and metastasis. Sorting out the various modes of action and defining their relative contribution in the context of tumor and host tissue as a heterogeneous target will therefore be crucial to understand the multi facetted effects of PPARgamma. This will be paramount if the potent biological activity of PPARgamma agonists are to be harnessed for cancer therapy.

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  • PPARγ is currently considered a potential target for both chemoprevention and cancer therapy based on preclinical studies.

    “In vitro studies indicate that PPARγ agonists have several anti-cancer activities, such as inhibiting growth and inducing apoptosis and cell differentiation (97), and PPARγ is currently considered a potential target for both chemoprevention and cancer therapy based on other preclinical studies (98,99).”

    From Diabetes and Cancer (2010) · cites this paper as [98]

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Authors
Panigraphy, D., Huang, S., Kieran, M. W., & Kaipainen, A.
Affiliations
Harvard University (US)
ORCID
Venue
Cancer Biology & Therapy
Publisher
Informa UK Limited
Published
2005-07
Volume
4
Issue
7
Pages
687-693
ISSN
  • 1538-4047 (ISSN-L)
  • 1555-8576
DOI
10.4161/cbt.4.7.2014
OpenAlex
W2063373049
Cited by
137
References
0
Citations by year
2026: 2 · 2025: 3 · 2024: 7 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 4 · 2019: 3 · 2018: 1 · 2017: 6 · 2016: 3 · 2015: 3 · 2014: 8 · 2013: 8 · 2012: 8
FWCI
1.16
Type
journal article
Language
en
Open access
Locations
  • Cancer Biology & Therapy (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
PPARγ, tumor angiogenesis, metastasis, PPARγ agonists, PPARγ antagonist, inflammation, tumor microenvironment, stromal changes, angiogenesis inhibition, anti-inflammatory activity, carcinogenesis, cancer therapy
MeSH terms
Humans, Neoplasm Metastasis, Neoplasms, Neovascularization, Pathologic, Angiogenesis Inhibitors, PPAR gamma

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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.

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