# Engineered bone matrix models for understanding breast cancer skeletal metastasis

**Authors:** Kylie M. Persson, Matthew A. Whitman, Claudia Fischbach

PMC · DOI: 10.1007/s10555-025-10310-1 · Cancer Metastasis Reviews · 2026-01-24

## TL;DR

This review explores how changes in bone matrix affect breast cancer spread to bones and highlights new engineered models to better understand and treat this condition.

## Contribution

The paper introduces engineered bone matrix models as a novel approach to study the role of bone matrix in breast cancer metastasis.

## Key findings

- Bone matrix changes are linked to both the progression and risk of breast cancer metastasis.
- Engineered models offer new insights into the biophysical and biochemical mechanisms of bone metastasis.
- Increasing bone density can protect against metastasis formation.

## Abstract

Bone is the most common site of metastasis in patients with advanced breast cancer and serves as a reservoir from which secondary metastases often originate. While research has traditionally focused on understanding the biochemical signals involved in bone metastasis, bone matrix changes are inextricably linked with its pathogenesis as well. Indeed, decreased bone matrix density is both a symptom of late-stage disease and a risk factor for metastasis formation. Vice versa, raising bone density protects against metastasis. How bone matrix controls metastatic outgrowth and progression and which biochemical or biophysical mechanisms are involved in these processes is poorly understood due in part to limitations in current models of bone metastasis. In this review, we discuss the role of bone matrix in the microenvironmental regulation of bone metastasis and its effect on mechanosignaling and highlight current and future engineered model systems that have the potential to yield new mechanistic insights to advance the clinical prognosis of breast cancer patients.

## Linked entities

- **Diseases:** breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432] {aka CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2}, TNFSF11 (TNF superfamily member 11) [NCBI Gene 8600] {aka CD254, ODF, OPGL, OPTB2, RANKL, TNLG6B}, NR2F1 (nuclear receptor subfamily 2 group F member 1) [NCBI Gene 7025] {aka BBOAS, BBSOAS, COUP-TFI, COUPTF1, EAR-3, EAR3}, ITGB1 (integrin subunit beta 1) [NCBI Gene 3688] {aka CD29, FNRB, GPIIA, MDF2, MSK12, VLA-BETA}, Pth (parathyroid hormone) [NCBI Gene 19226] {aka Pthp}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, RPS6KA5 (ribosomal protein S6 kinase A5) [NCBI Gene 9252] {aka MSK1, MSPK1, RLPK}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, SPP1 (secreted phosphoprotein 1) [NCBI Gene 6696] {aka BNSP, BSPI, ETA-1, OPN}
- **Diseases:** fracture (MESH:D050723), Breast Cancer (MESH:D001943), inflammatory (MESH:D007249), osteoid (MESH:D010017), prostate cancer (MESH:D011471), hypophosphatemic osteomalacia (MESH:D010018), bone (MESH:D001847), bone metastases (MESH:D009362), hypoxia (MESH:D000860), osteolytic lesion (MESH:D030981), tumorigenic (MESH:D002471), vitamin D (MESH:D014808), Tumor (MESH:D009369)
- **Chemicals:** carbonate (MESH:D002254), polymer (MESH:D011108), phosphate (MESH:D010710), oxygen (MESH:D010100), PLG (MESH:D011098), Ca2+ (-), glycosaminoglycans (MESH:D006025), PAA (MESH:C017645), mineral (MESH:D008903), calcium (MESH:D002118), calcium phosphate (MESH:C020243), HA (MESH:D017886)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12831698/full.md

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12831698/full.md

## References

9 references — full list in the complete paper: https://tomesphere.com/paper/PMC12831698/full.md

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Source: https://tomesphere.com/paper/PMC12831698