{
  "abstract": "Background: Colorectal cancer (CRC) liver metastasis (LM) is a leading cause of cancer-related death, with pre-metastatic niche (PMN) formation being critical for metastasis. Insulin-like growth factor binding protein 2 (IGFBP2) is overexpressed in metastatic CRC, but its role in intrahepatic fibrotic PMN formation and CRC-LM remains unclear.\n\nMethods: Bioinformatics analyses and tissue microarray samples were conducted to assess the expression level and prognostic significance of IGFBP2 in CRC patients. After overexpression of IGFBP2, its in vivo metastatic-promoting ability was evaluated by establishing a splenic injection liver metastasis model, while its in vitro malignant properties were assessed via colony formation, proliferation assay, flow cytometry, wound-healing assay and transwell assay. Furthermore, flow cytometry, RT-qPCR and ELISA were used to evaluate the effect of IGFBP2 overexpression on the polarization of intrahepatic macrophages. In addition, Western blot and immunofluorescence were performed to detect the effect of M2-polarized macrophages on hepatic stellate cells (HSCs). Finally, the splenic injection liver metastasis model was treated with CWI1-2 (IGFBP2 inhibitor) or pirfenidone (PFD, a TGF-β signaling modulator), and the therapeutic effects were observed.\n\nResults: We found that IGFBP2 is overexpressed in CRC tissues, correlating with poor prognosis. Meanwhile, IGFBP2 overexpression significantly promotes CRC-LM progression in vivo. Mechanistically, it drives M2 polarization of intrahepatic macrophages to boost TGF-β secretion. Subsequently, TGF-β activates HSCs, elevates the deposition of extracellular matrix (α-SMA, COL1, FN), and ultimately contributes to the development of intrahepatic fibrotic PMN. Notably, CWI-2 or PFD could suppress CRC-LM, with combined treatment showing synergistic effects both in vitro and in vivo.\n\nConclusions: IGFBP2 is highly expressed in CRC and correlated with patient prognosis. CRC-derived IGFBP2 drives intrahepatic fibrotic PMN formation via intrahepatic macrophages M2 polarization and TGF-β-mediated HSCs activation, which in turn facilitates CRC-LM. Furthermore, selective targeting of the process of intrahepatic PMN formation holds promise as a viable strategy for the prevention and treatment of CRC-LM.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12967-026-08726-6.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Radiology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062 China",
    "Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062 China",
    "Department of Respiratory Medicine, Xiamen TCM Hospital Affiliated to Fujian, University of Traditional Chinese Medicine, Xiamen, 361015 China",
    "Department of General Surgery, Shanghai Putuo People’s Hospital, Tongji University School of Medicine, Shanghai, 200060 China",
    "Shanghai Key Laboratory of Wearable Robotics and Human-Machine Interaction, Shanghai, 201804 China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jing Shang"
    },
    {
      "affs": [
        1
      ],
      "name": "Qin Yuan"
    },
    {
      "affs": [
        2
      ],
      "name": "Yuhua Lin"
    },
    {
      "affs": [
        1
      ],
      "name": "Jiahua Yang"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Peihao Yin"
    },
    {
      "affs": [
        1
      ],
      "name": "Wei Li",
      "orcid": "0000-0003-3694-8621"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/17etzc91dwszz.bib",
  "cited_by": 0,
  "doi": "10.1186/s12967-026-08726-6",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13746430/",
  "id": "17etzc91dwszz",
  "issns": [
    "1479-5876"
  ],
  "landing_url": "https://doi.org/10.1186/s12967-026-08726-6",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2730|Cancer Cells and Metastasis"
    ]
  ],
  "openalex": "W7202071904",
  "pdf_url": null,
  "pmcid": "PMC13746430",
  "pmid": "43000390",
  "published": "2026-08-10",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/17etzc91dwszz.ris",
  "sources": [
    {
      "first_seen": "2026-11-11T12:23:46Z",
      "native_id": "PMC13746430",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12967-026-08726-6"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Cells and Metastasis",
      "subfield": "oncology"
    }
  ],
  "title": "Colorectal cancer-derived IGFBP2 promotes liver metastasis by driving intrahepatic fibrotic pre-metastatic niche formation",
  "title_text": "Colorectal cancer-derived IGFBP2 promotes liver metastasis by driving intrahepatic fibrotic pre-metastatic niche formation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-13T12:22:51Z",
  "url": "https://research.draconitic.com/paper/17etzc91dwszz",
  "venue": "Journal of Translational Medicine",
  "versions": []
}