2. Academic Validation
  3. Micro-Organ Chip Deciphers Tumor-Derived G-CSF as Remote Commander of Lung Pre-Metastatic Niche via VEGFA-KDR Cascade

Micro-Organ Chip Deciphers Tumor-Derived G-CSF as Remote Commander of Lung Pre-Metastatic Niche via VEGFA-KDR Cascade

  • Adv Sci (Weinh). 2025 Nov 22:e18584. doi: 10.1002/advs.202518584.
Jingxin Zhang 1 2,  Xiaoying Huang 1,  Lingchuan Ma 1,  Zixing Chen 1,  Tianyao Li 2 3,  Lijian Wang 1,  Yutong Guo 1,  Hu Xu 2 4,  Junqi Li 5 6,  Jiang-Jiang Qin 7,  Xiang Wang 8,  Yuhong Cao 2,  Kai Miao 1 9 10
Affiliations

Affiliations

  • 1 Faculty of Health Sciences, University of Macau, Macau SAR, 519000, China.
  • 2 CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, 100190, China.
  • 3 University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 4 College of Ecology, Lanzhou University, Lanzhou, 730000, China.
  • 5 Clinical Research and Translational Medicine Department, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, China.
  • 6 Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, Henan, 450000, China.
  • 7 Center for Innovative Drug Research, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310018, China.
  • 8 Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100032, China.
  • 9 MOE Frontier Science Centre for Precision Oncology, University of Macau, Macau SAR, 519000, China.
  • 10 Zhuhai UM Science & Technology Research Institute, Hengqin, 519031, China.
PMID: 41275332 DOI: 10.1002/advs.202518584
Abstract

Metastasis is the leading cause of cancer-related mortality. During metastatic progression, distant organs form a pre-metastatic niche (PMN), creating a permissive microenvironment that facilitates circulating tumor cell (CTC) colonization. To investigate pulmonary PMN formation in breast Cancer, a micro-organ chip is employed that enables contact-independent coculture of tumor and lung tissues. This model reveals that PMN formation is governed by tumor-secreted factors without requiring direct tumor cell contact and exhibits non-tumor-type specificity. It is found that coculture with tumor tissue upregulates vascular endothelial growth factor (VEGF) receptor-2 (VEGFR2/KDR) in lung capillary cells. Through integrated single-cell RNA Sequencing and cytokine array analysis, granulocyte colony stimulating factor (G-CSF) is identified as a key tumor-derived mediator that modulates the pre-metastatic niche through activating the VEGFA-KDR signaling axis in the lung, thereby promoting angiogenesis and PMN development. This study highlights the G-CSF-KDR axis as a potential therapeutic target for inhibiting breast Cancer metastasis.

Keywords

G‐CSF; KDR; angiogenesis; micro‐organ chip; pre‐metastatic niche.

Figures
Products