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Models of Bone Metastasis
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Osteoblasts in bone metastasis: Key players in the tumor microenvironment and therapeutic targets

Lingxiao Jin1, Zhenxuan Shao1, Zhaoming Ye1

  • 1Orthopedic Oncology Services, Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China; Orthopedic Research Institute, Zhejiang University, Hangzhou 310009, China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou 310009, China; Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou 310009, China.

Biochimica Et Biophysica Acta. Reviews on Cancer
|August 31, 2025
PubMed

Insights

Osteoblasts play a critical role in bone metastasis by influencing tumor cell attraction, dormancy, and outgrowth. Targeting osteoblast interactions offers new strategies for bone cancer therapy.

Area of Science:

  • Oncology
  • Cell Biology
  • Cancer Metastasis

Background:

  • Osteoblasts are key regulators of bone metabolism and are increasingly recognized as important players in the bone tumor microenvironment (TME).
  • Their specific roles in promoting bone metastasis progression are not fully understood.
  • Existing research suggests osteoblasts significantly influence various stages of skeletal tumor development.

Purpose of the Study:

  • To elucidate the multifaceted roles of osteoblasts in orchestrating bone metastasis.
  • To detail the stage-specific interactions between osteoblasts and tumor cells.
  • To explore therapeutic strategies targeting osteoblast-tumor cell communication.

Main Methods:

  • Review of recent studies on osteoblast function in bone metastasis.
  • Analysis of molecular signaling pathways involved in osteoblast-tumor cell interactions (e.g., CXCL12/CXCR4, TGFβ2, BMP7, N-cadherin).
  • Examination of osteoblast's influence on immune cell activity and macrophage polarization within the TME.

Main Results:

  • Osteoblasts attract tumor cells, remodel the niche, and promote therapy resistance during early colonization and dormancy.
  • They drive metastatic outgrowth via metabolic coupling and mTOR activation.
  • Osteoblasts modulate the TME by suppressing anti-tumor immunity and promoting immune evasion.

Conclusions:

  • Osteoblasts are central regulators of bone metastasis progression through direct and indirect mechanisms.
  • Tumor-derived signals reprogram osteoblasts to support tumor growth.
  • Targeting osteoblast-mediated pathways presents a promising therapeutic avenue for bone cancers.
Keywords:
Bone metastasisMicroenvironmentOsteoblasts

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