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  3. Pericyte signaling via soluble guanylate cyclase shapes the vascular niche and microenvironment of tumors

Pericyte signaling via soluble guanylate cyclase shapes the vascular niche and microenvironment of tumors

  • EMBO J. 2024 Mar 25. doi: 10.1038/s44318-024-00078-5.
Jing Zhu # 1 2,  Wu Yang # 3 4,  Jianyun Ma # 2 5,  Hao He # 1 2,  Zhen Liu # 2 5 6,  Xiaolan Zhu 1 2,  Xueyang He 1 2,  Jing He 1 2,  Zhan Chen 7,  Xiaoliang Jin 8,  Xiaohong Wang 9,  Kaiwen He 1 2 10,  Wu Wei 11 12,  Junhao Hu 13 14 15
Affiliations

Affiliations

  • 1 Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
  • 2 University of Chinese Academy of Sciences, Beijing, China.
  • 3 Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China. wuyang@shsci.org.
  • 4 University of Chinese Academy of Sciences, Beijing, China. wuyang@shsci.org.
  • 5 CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.
  • 6 Lingang Laboratory, Shanghai, China.
  • 7 Pathology Department, Cixi People's Hospital, Zhejiang, China.
  • 8 Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 9 Department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
  • 10 Shanghai Key Laboratory of Aging Studies, Shanghai, China.
  • 11 CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China. wuwei@lglab.ac.cn.
  • 12 Lingang Laboratory, Shanghai, China. wuwei@lglab.ac.cn.
  • 13 Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China. jhhu@sioc.ac.cn.
  • 14 University of Chinese Academy of Sciences, Beijing, China. jhhu@sioc.ac.cn.
  • 15 Shanghai Key Laboratory of Aging Studies, Shanghai, China. jhhu@sioc.ac.cn.
  • # Contributed equally.
PMID: 38528180 DOI: 10.1038/s44318-024-00078-5
Abstract

Pericytes and endothelial cells (ECs) constitute the fundamental components of blood vessels. While the role of ECs in tumor angiogenesis and the tumor microenvironment is well appreciated, pericyte function in tumors remains underexplored. In this study, we used pericyte-specific deletion of the nitric oxide (NO) receptor, soluble Guanylate Cyclase (sGC), to investigate via single-cell RNA Sequencing how pericytes influence the vascular niche and the tumor microenvironment. Our findings demonstrate that pericyte sGC deletion disrupts EC-pericyte interactions, impairing Notch-mediated intercellular communication and triggering extensive transcriptomic reprogramming in both pericytes and ECs. These changes further extended their influence to neighboring cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) through paracrine signaling, collectively suppressing tumor growth. Inhibition of pericyte sGC has minimal impact on quiescent vessels but significantly increases the vulnerability of angiogenic tumor vessels to conventional anti-angiogenic therapy. In conclusion, our findings elucidate the role of pericytes in shaping the tumor vascular niche and tumor microenvironment and support pericyte sGC targeting as a promising strategy for improving anti-angiogenic therapy for Cancer treatment.

Keywords

Pericyte; Soluble Guanylate Cyclase; Tumor Microenvironment; Vascular Niche.

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