Pericyte Depletion Results in Hypoxia-Associated Epithelial-to-Mesenchymal Transition and Metastasis Mediated by Met Signaling Pathway
Open accessAbstract
The functional role of pericytes in cancer progression remains unknown. Clinical studies suggest that low numbers of vessel-associated pericytes correlated with a drop in overall survival of patients with invasive breast cancer. Using genetic mouse models or pharmacological inhibitors, pericyte depletion suppressed tumor growth but enhanced metastasis. Pericyte depletion was further associated with increased hypoxia, epithelial-to-mesenchymal transition (EMT), and Met receptor activation. Silencing of Twist or use of a Met inhibitor suppressed hypoxia and EMT/Met-driven metastasis. In addition, poor pericyte coverage coupled with high Met expression in cancer cells speculates the worst prognosis for patients with invasive breast cancer. Collectively, our study suggests that pericytes within the primary tumor microenvironment likely serve as important gatekeepers against cancer progression and metastasis.
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Therapeutic targets involving pericytes may exacerbate tumor metastasis.
“others indicated that therapeutic targets involving pericytes may exacerbate the process of tumor metastasis [31–34].”
From Tumor microenvironment complexity and therapeutic implications at a glance (2020) · cites this paper as [34]
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- Authors
- Cooke, V. G., LeBleu, V. S., Keskin, D., Khan, Z., O'Connell, J. T., Teng, Y., Duncan, M. B., Xie, L., Maeda, G., Vong, S., Sugimoto, H., Rocha, R. M., Damascena, A., Brentani, R. R., & Kalluri, R.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- AC Camargo Hospital (BR)
- Corresponding author
- Kalluri, Raghu
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 21
- Issue
- 1
- Pages
- 66-81
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC3999522
- OpenAlex
- W1562355542
- Cited by
- 530
- References
- 81
- Citations by year
- 2026: 12 · 2025: 21 · 2024: 24 · 2023: 25 · 2022: 32 · 2021: 41 · 2020: 48 · 2019: 26 · 2018: 45 · 2017: 44 · 2016: 45 · 2015: 46 · 2014: 50 · 2013: 42 · 2012: 28
- FWCI
- 21.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- Israel National Road Safety Authority
- National Institute of Diabetes and Digestive and Kidney Diseases (2T32DK007760-11, 5F32DK082119-02, 5T32CA081156-08)
- National Institutes of Health (CA125550, DK81576, CA151925, CA155370, CA163191, DK55001)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- pericytes, tumor hypoxia, epithelial-mesenchymal transition, metastasis, C-MET signaling, invasive breast cancer, tumor microenvironment, Twist, MET inhibitors
- MeSH terms
- Imatinib Mesylate, Sorafenib, Sunitinib, Crizotinib, Animals, Antineoplastic Agents, Benzamides, Benzenesulfonates, Breast Neoplasms, Female, Humans, Indoles, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Neoplasm Metastasis, Niacinamide, Phenylurea Compounds, Piperazines, Piperidines, Pyrazoles, Pyridines, Pyrimidines, Pyrroles, Tumor Cells, Cultured, Signal Transduction, Cell Hypoxia, Proto-Oncogene Proteins c-met, Pericytes, Cell Line, Tumor, Protein Kinase Inhibitors, Mice, Hypoxia-Inducible Factor 1, alpha Subunit, Epithelial-Mesenchymal Transition
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