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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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Induced Tumor-Suppressing (iTS) Cell-Based Approach for Protecting the Bone from Advanced Prostate Cancer.

Shengzhi Liu1,2, Di Wu2,3, Kazumasa Minami4

  • 1School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China.

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|February 27, 2026
PubMed
Summary

Researchers developed an induced tumor-suppressing (iTS) cell therapy to protect bone from advanced prostate cancer. Extracellular Moesin (MSN) protein was identified as a key therapeutic agent, inhibiting cancer growth and bone damage.

Keywords:
CD44Lrp5MSCMoesinboneiTS cellsosteocytesprostate cancer

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Area of Science:

  • Oncology
  • Bone Biology
  • Cell Therapy

Background:

  • Advanced prostate cancer commonly metastasizes to bone, leading to significant morbidity.
  • Current therapies for bone metastasis in prostate cancer are limited and often ineffective.

Purpose of the Study:

  • To develop a novel cell-based therapy for bone metastasis in advanced prostate cancer.
  • To identify new therapeutic targets and tumor-suppressing proteins.

Main Methods:

  • Utilized an induced tumor-suppressing (iTS) cell-based approach to generate tumor-suppressing proteins and conditioned medium (CM).
  • Investigated the role of Lrp5 and β-catenin in converting various cell types into iTS cells.
  • Analyzed CM from Lrp5-overexpressing osteocytes for therapeutic potential.
  • Employed whole-genome proteomics to identify key proteins in CM.
  • Used FRET live-cell imaging to elucidate the mechanism of action of Moesin (MSN).

Main Results:

  • Lrp5 conditional knockout mice exhibited severe bone loss, while osteocyte-derived CM from Lrp5-overexpressing cells rescued tumor-induced bone damage.
  • Moesin (MSN) was identified as an extracellular tumor-suppressing protein enriched in CM.
  • Extracellular MSN inhibited tumor growth by interacting with CD44, reducing Src tyrosine kinase activity and nuclear β-catenin localization.

Conclusions:

  • An iTS cell-based approach can protect bone from prostate cancer metastasis.
  • Moesin (MSN) is a potent extracellular tumor-suppressing protein with therapeutic potential against bone metastasis.