Engineering the early bone metastatic niche through human vascularized immuno bone minitissues

Area of Science:

• Oncology
• Biomedical Engineering
• Cancer Metastasis Research

Background:

• Bone metastases affect 65%-80% of advanced breast cancer patients.
• Current 2D *in vitro* models and animal studies fail to replicate the complex bone microenvironment and drug responses.
• This leads to frequent failures in pre-clinical drug testing.

Purpose of the Study:

• To develop a 3D metastatic bone minitissue (MBm) that recapitulates the bone metastatic niche.
• To investigate breast cancer cell (CC) interactions within this microenvironment.
• To assess the predictive value of the MBm for anti-cancer drug efficacy.

Main Methods:

• A 3D MBm was engineered with human osteoblasts, osteoclasts, macrophages, endothelial cells, and breast CCs.
• The MBm's ability to mimic key features of the bone metastatic niche was evaluated.
• Organ-specific metastasis and drug responses were compared between bone and muscle minitissues.

Main Results:

• The MBm successfully replicated the bone metastatic niche, including altered macrophage polarization and vascular architecture.
• It induced CC micrometastases and osteomimicry, reflecting organ-specific bone metastasis.
• Drug efficacy testing revealed significantly higher required doses for doxorubicin and rapamycin in MBm compared to CC monocultures.

Conclusions:

• The 3D MBm serves as a reliable tool for studying metastasis in the bone microenvironment.
• It offers a more accurate platform for predicting drug effects on metastatic bone disease.
• This model can enhance the translation of pre-clinical findings to clinical applications.