Cited by 345Angiogenesis and VEGF in CancerBarrier Structure and Function StudiesCancer Cells and Metastasis

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Pericytes limit tumor cell metastasis

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Xian, X.·2006·Journal of Clinical Investigation

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Abstract

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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Authors: Xian, X.
Affiliations: Lund University (SE)
Corresponding author: Xian, X.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2006-03-01
Volume: 116
Issue: 3
Pages: 642-651
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci25705
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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Pericytes limit tumor cell metastasis

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