Pericytes limit tumor cell metastasis
Open accessAbstract
Previously we observed that neural cell adhesion molecule (NCAM) deficiency in beta tumor cells facilitates metastasis into distant organs and local lymph nodes. Here, we show that NCAM-deficient beta cell tumors grew leaky blood vessels with perturbed pericyte-endothelial cell-cell interactions and deficient perivascular deposition of ECM components. Conversely, tumor cell expression of NCAM in a fibrosarcoma model (T241) improved pericyte recruitment and increased perivascular deposition of ECM molecules. Together, these findings suggest that NCAM may limit tumor cell metastasis by stabilizing the microvessel wall. To directly address whether pericyte dysfunction increases the metastatic potential of solid tumors, we studied beta cell tumorigenesis in primary pericyte-deficient Pdgfb(ret/ret) mice. This resulted in beta tumor cell metastases in distant organs and local lymph nodes, demonstrating a role for pericytes in limiting tumor cell metastasis. These data support a new model for how tumor cells trigger metastasis by perturbing pericyte-endothelial cell-cell interactions.
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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 [31]
The Abstract and Discussion (page unavailable) report that pericyte dysfunction increased tumor-cell dissemination in a genetic mouse model, supporting the concern that disrupting pericytes could worsen metastasis. The paper does not report that a therapeutic intervention targeting pericytes exacerbated metastasis; that part is an inference from its findings. (LLM, conf=0.82)
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- Authors
- Xian, X.
- Affiliations
- Lund University (SE)
- Corresponding author
- Xian, X.
- Venue
- Journal of Clinical Investigation
- Published
- 2006-03-01
- Volume
- 116
- Issue
- 3
- Pages
- 642-651
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1361347
- OpenAlex
- W2082320957
- Cited by
- 345
- References
- 47
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 8 · 2023: 9 · 2022: 18 · 2021: 13 · 2020: 19 · 2019: 18 · 2018: 18 · 2017: 18 · 2016: 27 · 2015: 22 · 2014: 21 · 2013: 31 · 2012: 23
- FWCI
- 6.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Swedish Cancer Foundation
- Cancer Research UK
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- pericytes, metastasis, CD56, beta cell tumors, pericyte-endothelial interactions, extracellular matrix deposition, lymph node metastasis, fibrosarcoma
- MeSH terms
- Animals, Cell Communication, Endothelium, Vascular, Fibrosarcoma, Adenoma, Islet Cell, Mice, Inbred C57BL, Neoplasm Metastasis, Neovascularization, Pathologic, Pancreatic Neoplasms, Mice, Knockout, Neural Cell Adhesion Molecules, Pericytes, Mice
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