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Updated: Feb 28, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
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.
Abstract:
Advanced prostate cancer frequently metastasizes to bone, but no effective therapy exists. To seek a novel treatment option and identify a new drug target, we took an induced tumor-suppressing (iTS) cell-based approach and produced tumor-suppressing proteins and conditioned medium (CM). Notably, the overexpression of Lrp5 and β-catenin, as well as the pharmacological Wnt activator, converted osteocytes, Murine mesenchymal stem cells, mononuclear cells, and monocytes into iTS cells. While Lrp5 conditional knockout mice presented severe bone loss, Lrp5-overexpressing osteocyte-derived CM rescued tumor-induced bone damage. Whole-genome proteomics analysis revealed that Moesin (MSN), which acted as an oncogene in tumor cells, was enriched in CM as an extracellular tumor-suppressing protein. Its anti-tumor action was mediated primarily by the interaction with CD44. Consistently, FRET live-cell imaging demonstrated that extracellular MSN reduced Src tyrosine kinase activity and nuclear localization of β-catenin. Collectively, we demonstrated herein the iTS cell-based approach to protect bone from prostate cancer and showed MSN as a potent extracellular tumor-suppressing protein.
Insights
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.
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.
