Faculty, Staff and Student Publications
Language
English
Publication Date
9-1-2024
Journal
Nature Cancer
DOI
10.1038/s43018-024-00813-1
PMID
39289595
PMCID
PMC11987010
PubMedCentral® Posted Date
9-17-2025
PubMedCentral® Full Text Version
Author MSS
Abstract
Carcinomas are associated with metastasis to specific organs while sparing others. Breast cancer presents with lung metastasis but rarely kidney metastasis. Using this difference as an example, we queried the mechanism(s) behind the proclivity for organ-specific metastasis. We used spontaneous and implant models of metastatic mammary carcinoma coupled with inflammatory tissue fibrosis, single-cell sequencing analyses and functional studies to unravel the causal determinants of organ-specific metastasis. Here we show that lung metastasis is facilitated by angiopoietin 2 (Ang2)-mediated suppression of lung-specific endothelial tight junction protein Claudin 5, which is augmented by the inflammatory fibrotic microenvironment and prevented by anti-Ang2 blocking antibodies, while kidney metastasis is prevented by non-Ang2-responsive Claudins 2 and 10. Suppression of Claudins 2 and 10 was sufficient to induce the emergence of kidney metastasis. This study illustrates the influence of organ-specific vascular heterogeneity in determining organotropic metastasis, independent of cancer cell-intrinsic mechanisms.
Keywords
Animals, Female, Mice, Claudins, Tight Junctions, Kidney Neoplasms, Humans, Lung Neoplasms, Tumor Microenvironment, Breast Neoplasms, Cell Line, Tumor, Neoplasm Metastasis
Published Open-Access
yes
Recommended Citation
Zhou, Xunian; LeBleu, Valerie S; Fletcher-Sananikone, Eliot; et al., "Vascular Heterogeneity of Tight Junction Claudins Guides Organotropic Metastasis" (2024). Faculty, Staff and Student Publications. 5935.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5935
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