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Related Experiment Video

Updated: May 13, 2025

Models of Bone Metastasis
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Patient-Derived Breast Cancer Bone Metastasis In Vitro Model Using Bone-Mimetic Nanoclay Scaffolds.

Haneesh Jasuja1, Farid Solaymani Mohammadi2, Jiha Kim2

  • 1Department of Civil Construction and Environmental Engineering, North Dakota State University, Fargo, ND 58108, USA.

Journal of Tissue Engineering and Regenerative Medicine
|April 14, 2025
PubMed
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This study validates a 3D in vitro model for breast cancer bone metastasis using patient-derived cells. The model successfully mimics bone lesions by showing how cancer cells affect bone growth via specific signaling pathways.

Area of Science:

  • Oncology
  • Cell Biology
  • Biomedical Engineering

Background:

  • Breast cancer bone metastasis significantly worsens patient prognosis.
  • Developing reliable models for studying metastasis is crucial for improving patient outcomes.
  • Previous work established a 3D in vitro model using human mesenchymal stem cells (hMSCs) and breast cancer cell lines.

Purpose of the Study:

  • To test and validate a previously developed 3D in vitro breast cancer bone metastasis model.
  • To investigate the effects of patient-derived breast cancer cell lines (NT013 and NT023) on bone growth within this model.
  • To compare the model's performance with different cancer cell line characteristics.

Main Methods:

  • Utilized a 3D in vitro model comprising hMSCs and patient-derived breast cancer cell lines (NT013, NT023).

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  • Investigated the mesenchymal to epithelial transition (MET) of cancer cells within the bone microenvironment.
  • Analyzed the impact of cancer cell-secreted cytokines (ET-1 and DKK-1) on Wnt-related gene expression and the osteogenic pathway in hMSCs.

    • Main Results:

    • Patient-derived NT013 (hormone-positive) and NT023 (triple-negative) cells underwent MET and formed tumors, consistent with prior findings.
    • NT013 cells stimulated the osteogenic pathway via ET-1, leading to Wnt gene upregulation in hMSCs.
    • NT023 cells abrogated the osteogenic pathway via DKK-1, causing Wnt gene downregulation in hMSCs.
    • The model successfully mimicked distinct bone lesion types observed in breast cancer patients.

    Conclusions:

    • The 3D in vitro model is effective for studying breast cancer bone metastasis using diverse patient-derived cell lines.
    • The model accurately recapitulates the differential effects of cancer cells on bone remodeling.
    • This validated model can aid in understanding metastasis mechanisms and developing targeted therapies for bone lesions.