Nature Communications (Aug 2025)
Pericytes promote metastasis by regulating tumor local vascular tone and hemodynamics
- Xiaobo Li,
- Sishan Yan,
- Xiaoyu Wu,
- Qun Miao,
- Dong Zhang,
- Wenfeng Mai,
- Shuai Han,
- Zhongshun Tang,
- Mingfang Ye,
- Shuo Zhang,
- Ji-an Wei,
- Jinghua Pan,
- Dandan Huang,
- Shenghui Qiu,
- Zhan Zhao,
- Xiaotong Zhong,
- Maohua Huang,
- Ming Qi,
- Junqiu Zhang,
- Chenran Wang,
- Jingwen Xie,
- Sheng Wang,
- Oscar Junhong Luo,
- Dongmei Zhang,
- Wencai Ye,
- Minfeng Chen
Affiliations
- Xiaobo Li
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University
- Sishan Yan
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University
- Xiaoyu Wu
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University
- Qun Miao
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University
- Dong Zhang
- Department of Medical Imaging Center, The First Affiliated Hospital, Jinan University
- Wenfeng Mai
- Department of Medical Imaging Center, The First Affiliated Hospital, Jinan University
- Shuai Han
- Department of Gastrointestinal Surgery, General Surgery Center, Zhujiang Hospital, Southern Medical University
- Zhongshun Tang
- Department of Gastrointestinal Surgery, General Surgery Center, Zhujiang Hospital, Southern Medical University
- Mingfang Ye
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University
- Shuo Zhang
- School of Instrument Science and Engineering, Southeast University
- Ji-an Wei
- Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University
- Jinghua Pan
- Department of General Surgery, The First Affiliated Hospital of Jinan University
- Dandan Huang
- The Sixth Affiliated Hospital, Sun Yet-sen University
- Shenghui Qiu
- Department of General Surgery, The First Affiliated Hospital of Jinan University
- Zhan Zhao
- Department of General Surgery, The First Affiliated Hospital of Jinan University
- Xiaotong Zhong
- College of Pharmacy, Jinan University
- Maohua Huang
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University
- Ming Qi
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University
- Junqiu Zhang
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University
- Chenran Wang
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University
- Jingwen Xie
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University
- Sheng Wang
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University
- Oscar Junhong Luo
- Department of Systems Biomedical Sciences, School of Medicine, Jinan University
- Dongmei Zhang
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University
- Wencai Ye
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University
- Minfeng Chen
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University
- DOI
- https://doi.org/10.1038/s41467-025-62475-6
- Journal volume & issue
-
Vol. 16,
no. 1
pp. 1 – 20
Abstract
Abstract Hemodynamics are important for survival and extravasation of circulating tumor cells, whereas the effects of hemodynamics on tumor cell intravasation remain mostly unknown. Here, we show that colorectal cancer patients with liver metastasis are characterized by increased diameter and blood flow in the primary tumor compared with non-metastatic patients. A subpopulation of NKX2-3high tumor pericytes (TPCs) in the primary tumor is associated with hematogenous metastasis of patients. Mechanistically, long noncoding RNA NEAT1-enriched extracellular vesicles induce NKX2-3 upregulation in TPCs. NKX2-3 suppresses calcium influx in TPCs via PDE1C/cAMP/PKA signaling axis, inducing tumor vasodilation and increasing blood flux and vascular leakage. Genetic deletion of Nkx2-3 or pharmacological blocking the transcriptional activity of NKX2-3 in TPCs with designed peptide induce tumor local vasoconstriction and decrease blood flow to mitigate tumor metastasis. These findings reveal that TPCs-regulated vasodilation and hemodynamics facilitate tumor metastasis, and provide a potential prognostic marker and therapeutic strategy for tumor metastasis.
