journal article·2026-02Open access

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

Jingxin Zhang, Xiaoying Huang, Lingchuan Ma, Zixing Chen, Tianyao Li, Lijian Wang, Yutong Guo, Hu Xu, Junqi Li, Jiang‐Jiang Qin, Xiang Wang, Yuhong Cao, Kai Miao

Advanced Science· Volume 13· Issue 7

Abstract

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.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Cancer Cells and Metastasis · Single-cell and spatial transcriptomics · 3D Printing in Biomedical Research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Faculty of Health Sciences University of Macau Macau SAR 519000 China

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety National Center for Nanoscience and Technology Chinese Academy of Sciences Beijing 100190 China

University of Chinese Academy of Sciences Beijing 100049 China

College of Ecology Lanzhou University Lanzhou 730000 China

Clinical Research and Translational Medicine Department The Third Affiliated Hospital of Zhengzhou University Zhengzhou Henan 450000 China

Tianjian Laboratory of Advanced Biomedical Sciences Zhengzhou University Zhengzhou Henan 450000 China

Center for Innovative Drug Research Hangzhou Institute of Medicine (HIM) Chinese Academy of Sciences Hangzhou Zhejiang 310018 China

Department of Medical Oncology Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100032 China

MOE Frontier Science Centre for Precision Oncology University of Macau Macau SAR 519000 China

Zhuhai UM Science & Technology Research Institute Hengqin 519031 China

Funding

National Key Research and Development Program of China · Fundo para o Desenvolvimento das Ciências e da Tecnologia · Universidade de Macau

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