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Coadaptation fostered by the SLIT2-ROBO1 axis facilitates liver metastasis of pancreatic ductal adenocarcinoma

Author

Listed:
  • Qing Li

    (Shanghai Jiao Tong University
    Shanghai Jiao Tong University)

  • Xiao-Xin Zhang

    (Shanghai Jiao Tong University
    Jiangsu University)

  • Li-Peng Hu

    (Shanghai Jiao Tong University)

  • Bo Ni

    (Shanghai Jiao Tong University)

  • Dong-Xue Li

    (Shanghai Jiao Tong University)

  • Xu Wang

    (Shanghai Jiao Tong University)

  • Shu-Heng Jiang

    (Shanghai Jiao Tong University)

  • Hui Li

    (Shanghai Jiao Tong University)

  • Min-Wei Yang

    (Shanghai Jiao Tong University)

  • Yong-Sheng Jiang

    (Shanghai Jiao Tong University)

  • Chun-Jie Xu

    (Shanghai Jiao Tong University)

  • Xue-Li Zhang

    (Shanghai Jiao Tong University)

  • Yan-Li Zhang

    (Shanghai Jiao Tong University)

  • Pei-Qi Huang

    (Shanghai Jiao Tong University)

  • Qin Yang

    (Shanghai Jiao Tong University)

  • Yang Zhou

    (Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Jian-ren Gu

    (Shanghai Jiao Tong University)

  • Gary Gui-Shan Xiao

    (Dalian University of Technology
    Creighton University Medical Center)

  • Yong-wei Sun

    (Shanghai Jiao Tong University)

  • Jun Li

    (Shanghai Jiao Tong University)

  • Zhi-Gang Zhang

    (Shanghai Jiao Tong University)

Abstract

To explore the mechanism of coadaptation and the potential drivers of pancreatic ductal adenocarcinoma (PDAC) metastasis to the liver, we study key molecules involved in this process and their translational value. Premetastatic niche (PMN) and macrometastatic niche (MMN) formation in a mouse model is observed via CT combined with 3D organ reconstruction bioluminescence imaging, and then we screen slit guidance ligand 2 (SLIT2) and its receptor roundabout guidance receptor 1 (ROBO1) as important factors. After we confirm the expression and distribution of SLIT2 and ROBO1 in samples from PDAC patients and several mouse models, we discover that SLIT2-ROBO1-mediated coadaptation facilitated the implantation and outgrowth of PDAC disseminated tumour cells (DTCs) in the liver. We also demonstrate the dependence receptor (DR) characteristics of ROBO1 in a follow-up mechanistic study. A neutralizing antibody targeting ROBO1 significantly attenuate liver metastasis of PDAC by preventing the coadaptation effect. Thus, we demonstrate that coadaptation is supported by the DR characteristics in the PMN and MMN.

Suggested Citation

  • Qing Li & Xiao-Xin Zhang & Li-Peng Hu & Bo Ni & Dong-Xue Li & Xu Wang & Shu-Heng Jiang & Hui Li & Min-Wei Yang & Yong-Sheng Jiang & Chun-Jie Xu & Xue-Li Zhang & Yan-Li Zhang & Pei-Qi Huang & Qin Yang , 2023. "Coadaptation fostered by the SLIT2-ROBO1 axis facilitates liver metastasis of pancreatic ductal adenocarcinoma," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36521-0
    DOI: 10.1038/s41467-023-36521-0
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    References listed on IDEAS

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