Pericytes promote metastasis by regulating tumor local vascular tone and hemodynamics
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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62475-6 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Xiaobo Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c481c33cc2e5481383a7c2b50bca9652 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-c481c33cc2e5481383a7c2b50bca96522025-08-20T03:43:14ZengNature PortfolioNature Communications2041-17232025-08-0116112010.1038/s41467-025-62475-6Pericytes promote metastasis by regulating tumor local vascular tone and hemodynamicsXiaobo Li0Sishan Yan1Xiaoyu Wu2Qun Miao3Dong Zhang4Wenfeng Mai5Shuai Han6Zhongshun Tang7Mingfang Ye8Shuo Zhang9Ji-an Wei10Jinghua Pan11Dandan Huang12Shenghui Qiu13Zhan Zhao14Xiaotong Zhong15Maohua Huang16Ming Qi17Junqiu Zhang18Chenran Wang19Jingwen Xie20Sheng Wang21Oscar Junhong Luo22Dongmei Zhang23Wencai Ye24Minfeng Chen25State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan UniversityState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan UniversityState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan UniversityState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan UniversityDepartment of Medical Imaging Center, The First Affiliated Hospital, Jinan UniversityDepartment of Medical Imaging Center, The First Affiliated Hospital, Jinan UniversityDepartment of Gastrointestinal Surgery, General Surgery Center, Zhujiang Hospital, Southern Medical UniversityDepartment of Gastrointestinal Surgery, General Surgery Center, Zhujiang Hospital, Southern Medical UniversityState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan UniversitySchool of Instrument Science and Engineering, Southeast UniversityKey Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan UniversityDepartment of General Surgery, The First Affiliated Hospital of Jinan UniversityThe Sixth Affiliated Hospital, Sun Yet-sen UniversityDepartment of General Surgery, The First Affiliated Hospital of Jinan UniversityDepartment of General Surgery, The First Affiliated Hospital of Jinan UniversityCollege of Pharmacy, Jinan UniversityState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan UniversityState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan UniversityState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan UniversityState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan UniversityState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan UniversityState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan UniversityDepartment of Systems Biomedical Sciences, School of Medicine, Jinan UniversityState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan UniversityState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan UniversityState Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan UniversityAbstract 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.https://doi.org/10.1038/s41467-025-62475-6 |
| spellingShingle | 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 Pericytes promote metastasis by regulating tumor local vascular tone and hemodynamics Nature Communications |
| title | Pericytes promote metastasis by regulating tumor local vascular tone and hemodynamics |
| title_full | Pericytes promote metastasis by regulating tumor local vascular tone and hemodynamics |
| title_fullStr | Pericytes promote metastasis by regulating tumor local vascular tone and hemodynamics |
| title_full_unstemmed | Pericytes promote metastasis by regulating tumor local vascular tone and hemodynamics |
| title_short | Pericytes promote metastasis by regulating tumor local vascular tone and hemodynamics |
| title_sort | pericytes promote metastasis by regulating tumor local vascular tone and hemodynamics |
| url | https://doi.org/10.1038/s41467-025-62475-6 |
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