{
  "abstract": "Vitamin D deficiency is associated with poor outcome in several cancers in humans, and administration of vitamin D or analogs has been shown to decrease tumor progression and metastasis in animal mammary cancer models. We previously demonstrated significant acceleration of carcinogenesis in vitamin D-deficient mouse mammary tumor virus-polyoma middle T (MMTV-PyMT) mammary cancer model as well as of its spontaneous metastasis to lungs. While vitamin D also plays a role in skeletal metastasis, detailed mechanisms of its promotion of bone invasion and metastatic events are not completely elucidated. In the present study we used tibially-injected MMTV-PyMT mammary tumor cells to analyse how dietary-induced vitamin D deficiency in non-immunodeficient FVB mice accelerates bone invasion. Mechanistically, we observed vitamin D deficiency to increase pro-inflammation cytokines and nestin expression in internal bone surface and marrow, and to increase epithelial-to-mesenchymal transition (EMT) through Zeb1 transcription factor. In vitro, treatment of MMTV-PyMT tumor cells with CXCL12 was observed to stimulate Zeb1 expression, and this effect was efficiently countered by 1,25(OH)2D treatment. Analysis of cytokines in MMTV-PyMT mammary tumor cells in vitro showed significant reduction in several pro-inflammatory cytokines with 1,25(OH)2D treatment (GM-CSF, ICAM-1, IL-1ra, IP-10, JE, MCP-5, MIP-1, MIP-1{beta}, MIP-2, RANTES and CXCL12), a crucial observation in view of the current evidence that inflammation is one of the hallmarks of cancer. Furthermore, vitamin D repleteness is associated with very high expression of Socs1 (suppressor of cytokine signalling 1), an inhibitor of JAK/STAT pathway which prevents excessive inflammatory responses and has a tumor-suppressive role. These findings provide a strong link between vitamin D deficiency and acceleration of inflammation-driven bone invasion, and nestin and EMT. The evidence suggests that vitamin D-repleteness in breast cancer patients could enhance the efficacy of co-administered therapies in preventing invasion of skeletal sites.",
  "abstract_shown": true,
  "affiliations": [
    "Research Institute of the MUHC"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "J. Li"
    },
    {
      "name": "A.-L. Luco"
    },
    {
      "name": "A. Camirand"
    },
    {
      "affs": [
        0
      ],
      "name": "R. Kremer"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/57v53pvn85v7n.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.02.748895",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.02.748895v1.full",
  "id": "57v53pvn85v7n",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.02.748895v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "2734|Vitamin D Research Studies"
    ]
  ],
  "openalex": "W7207584052",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.02.748895v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-02",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/57v53pvn85v7n.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:01Z",
      "native_id": "10.64898/2026.09.02.748895",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.02.748895v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Vitamin D counters bone invasion by mammary cancer through inhibition of inflammation and epithelial-to-mesenchymal transition",
  "title_text": "Vitamin D counters bone invasion by mammary cancer through inhibition of inflammation and epithelial-to-mesenchymal transition",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:01Z",
  "url": "https://research.draconitic.com/paper/57v53pvn85v7n",
  "venue": "bioRxiv",
  "versions": []
}