{
  "abstract": "Background: The Wnt signaling pathway drives tumor cell invasion, metastasis, and bone formation, making it a key mediator of prostate cancer (PCa) skeletal metastasis. Dickkopf-related protein 1 (DKK1) inhibits canonical Wnt signaling by binding to the Wnt co-receptor LRP5/6; the DKK1-binding receptors Kremen1/2 cooperate in this inhibition. We investigated whether targeting this axis affects early bone colonization in a subcutaneous PCa xenograft model, an approach that reflects spontaneous metastatic dissemination but is limited by low metastatic frequency and the requirement for immunodeficient hosts.\n\nMethods: Luc2/RGB-labelled PC-3 cells were implanted subcutaneously into male immunodeficient mice. DKK1 was neutralized with the humanized anti-DKK1 monoclonal antibody hDKN-01 during primary tumor growth (pre-OP) or following primary tumor surgical resection (post-OP). Further experiments used host mice with heterozygous Lrp5 gain-of-function mutation (Lrp5+/G170V) or knockout of Kremen1 (Krm1−/−), Kremen2 (Krm2−/−), or both. Bone metastatic burden was quantified using anti-luciferase immunohistochemistry on serial hindlimb sections. Serum DKK1 ELISA and bone histomorphometry confirmed treatment efficacy and genotype phenotypes.\n\nResults: hDKN-01 reduced serum DKK1 and increased trabecular bone volume, confirming biological activity, but did not affect tumor growth or bone metastatic burden in either treatment window. Lrp5+/G170V and Krm1/Krm2 double-KO mice showed expected bone phenotypes without altered bone colonization (detected in 13–33% of mice). Notably, Krm2−/− mice showed only single disseminated tumor cells in bone, with no outgrowing colonies (0% of mice).\n\nConclusions: Neither systemic neutralization of DKK1 nor Lrp5 mutation nor Krm1 or Krm1/Krm2 knockout had any effect on bone colonization of subcutaneous PC-3 xenografts in immunodeficient mice. In contrast, Krm2 knockout prevented the formation of colonizing bone metastases, apparently depending on the presence of Krm1.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Anatomy, University of Luebeck, Luebeck, Germany",
    "Institute of Anatomy and Experimental Morphology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany",
    "Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany",
    "Institute of Molecular Biology (IMB), Mainz, Germany",
    "Division of Molecular Embryology, DKFZ-ZMBH Alliance, Heidelberg, Germany",
    "Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "By Marie-Therese Haider"
    },
    {
      "affs": [
        1
      ],
      "name": "Vera Freytag"
    },
    {
      "affs": [
        2
      ],
      "name": "Anke Baranowsky"
    },
    {
      "affs": [
        0
      ],
      "name": "Farbod Bahreini"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Christof Niehrs"
    },
    {
      "affs": [
        5
      ],
      "name": "Thorsten Schinke"
    },
    {
      "affs": [
        5
      ],
      "name": "Michael Amling"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Tobias Lange"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/47mgeqw8tw0ya.bib",
  "cited_by": 0,
  "doi": "10.1016/j.jbo.2026.100814",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13742230/",
  "id": "47mgeqw8tw0ya",
  "issns": [
    "2212-1366",
    "2212-1374"
  ],
  "landing_url": "https://doi.org/10.1016/j.jbo.2026.100814",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Paper"
    ],
    [
      "openalex",
      "1312|Wnt/β-catenin signaling in development and cancer"
    ]
  ],
  "openalex": "W7224934547",
  "pdf_url": null,
  "pmcid": "PMC13742230",
  "pmid": "42997515",
  "published": "2026-10-30",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/47mgeqw8tw0ya.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T12:23:05Z",
      "native_id": "PMC13742230",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.jbo.2026.100814"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Wnt/β-catenin signaling in development and cancer",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Influence of the Dickkopf-related protein 1-(co)receptor axis on early bone colonization in a subcutaneous human prostate cancer xenograft model",
  "title_text": "Influence of the Dickkopf-related protein 1-(co)receptor axis on early bone colonization in a subcutaneous human prostate cancer xenograft model",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T12:23:05Z",
  "url": "https://research.draconitic.com/paper/47mgeqw8tw0ya",
  "venue": "Journal of Bone Oncology",
  "versions": []
}