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Updated: Jul 14, 2026
Models of Bone Metastasis
Published on: September 4, 2012
Studies of osteotropism on both sides of the breast cancer-bone interaction
Jodie Moreau1, Kristen M Anderson, Joshua R Mauney
1Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Abstract:
While important advances have been made in the treatment of breast cancer (BrCa), little progress has been made in developing therapies for metastasis to bone, a complication that signals entry of the disease into an incurable phase. The process of identifying genes and gene signatures of BrCa associated with metastasis has begun. In contrast, knowledge of the contributions of bone to tumor-stroma interaction is still rudimentary. We are performing research designed to elucidate the mechanisms by which human BrCa metastasizes to bone (osteotropism). With evidence mounting that there is mutual recognition of BrCa and bone, we are investigating osteotropism from both sides of the tumor-stroma interface. We created a novel "all human" model in which human bone is transplanted into immunodeficient (NOD/SCID) mice. Human BrCa cells are injected into the mammary fat pad. Metastases later appear as metastases in the human bone, but not mouse skeleton. The model recapitulates the metastatic sequence occurring in patients. Using DNA microarrays, we plan to identify putative osteotropic genes expressed by metastatic BrCa cells. We will test the hypothesis that distinct "tool kits" are used by BrCa metastasizing to human bone. In addition, using human tissue-engineered bone, we are identifying components within bone stroma essential for metastasis, and osteotropism genes expressed by bone in response to the presence of BrCa. We recently demonstrated that tissue-engineered bone based on a silk sponge platform is a target for human BrCa metastasis, even in preference to the mouse skeleton.
Insights
Researchers developed a novel model to study breast cancer (BrCa) bone metastasis. This "all human" system reveals specific genes and bone components involved in BrCa osteotropism, advancing understanding of incurable cancer spread.
Area of Science:
- Oncology
- Skeletal Biology
- Translational Research
Background:
- Breast cancer (BrCa) metastasis to bone signifies an incurable disease stage.
- Current understanding of bone's role in tumor-stroma interactions during metastasis is limited.
- Effective therapies for bone metastasis remain a critical unmet need.
Purpose of the Study:
- To elucidate the mechanisms of human BrCa metastasis to bone (osteotropism).
- To investigate the bidirectional tumor-stroma interactions between BrCa and bone.
- To identify genes and bone stromal components critical for BrCa bone metastasis.
Main Methods:
- Developed a novel "all human" xenograft model using human bone xenografts in immunodeficient mice.
- Injected human BrCa cells into the mammary fat pad of mice bearing human bone grafts.
- Utilized DNA microarrays to identify gene expression profiles in metastatic BrCa cells and bone tissues.
- Employed tissue-engineered bone on a silk sponge platform to assess metastatic tropism.
Main Results:
- The "all human" model successfully recapitulated human BrCa metastasis to human bone, not the mouse skeleton.
- Identified putative osteotropic genes in metastatic BrCa cells, suggesting distinct "tool kits" for bone metastasis.
- Demonstrated that tissue-engineered bone is a preferred target for human BrCa metastasis.
- Identified essential bone stroma components and BrCa-induced osteotropism genes.
Conclusions:
- The developed "all human" model is effective for studying BrCa bone metastasis mechanisms.
- Distinct molecular mechanisms and genetic "tool kits" are likely involved in BrCa osteotropism.
- Bone stroma plays a crucial role in facilitating BrCa metastasis to bone.
- Further research into these mechanisms may lead to novel therapeutic strategies for bone metastasis.
