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Updated: Jul 5, 2025

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Osteocyte mitochondria inhibit tumor development via STING-dependent antitumor immunity

Hao Zhou1,2,3, Wenkan Zhang1,2,3, Hengyuan Li2,3,4

  • 1Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Science Advances
|January 17, 2024
PubMed

Insights

Osteocytes protect against bone metastasis by transferring mitochondria to cancer cells, activating an antitumor response. Disrupting this transfer accelerates cancer progression in bone.

Area of Science:

  • Oncology
  • Cell Biology
  • Immunology

Background:

  • Bone metastasis is a common and challenging complication of cancer.
  • Osteocytes, the most abundant cells in bone, play a critical role in maintaining bone matrix.
  • The specific function of osteocytes in the context of bone metastasis remains largely undefined.

Purpose of the Study:

  • To investigate the role of osteocytes in bone metastasis.
  • To elucidate the mechanism by which osteocytes interact with metastatic cancer cells.
  • To identify potential therapeutic targets for preventing bone metastasis.

Main Methods:

  • Utilized genetic knockout models to specifically target mitochondrial Rho GTPase 1 (Rhot1) and mitochondrial mitofusin 2 (Mfn2) in osteocytes.
  • Examined the impact of these genetic modifications on tumor immunogenicity and cancer cell colonization in the bone matrix.
  • Analyzed the transfer of mitochondria from osteocytes to cancer cells and its effect on the cGAS/STING pathway.

Main Results:

  • Demonstrated that osteocytes transfer mitochondria to metastatic cancer cells.
  • Showed that this mitochondrial transfer triggers a cGAS/STING-mediated antitumor immune response.
  • Found that impairing mitochondrial transfer (by knocking out Rhot1 or Mfn2 in osteocytes) led to reduced tumor immunogenicity and accelerated bone metastasis progression.

Conclusions:

  • Osteocytes play a protective role against bone metastasis through mitochondria transfer to cancer cells.
  • The cGAS/STING pathway is activated by osteocyte-derived mitochondria, contributing to tumor suppression.
  • Targeting osteocyte mitochondria transfer presents a potential therapeutic strategy for inhibiting bone metastasis.

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