# Induced Tumor-Suppressing (iTS) Cell-Based Approach for Protecting the Bone from Advanced Prostate Cancer

## TL;DR

This paper introduces a new cell-based approach to protect bones from advanced prostate cancer by using tumor-suppressing cells and proteins.

## Contribution

The study introduces the iTS cell-based approach and identifies Moesin (MSN) as a novel extracellular tumor-suppressing protein.

## Key findings

- Lrp5 and β-catenin overexpression can convert various cells into iTS cells.
- Moesin (MSN) acts as an extracellular tumor-suppressing protein by interacting with CD44.
- Extracellular MSN reduces Src tyrosine kinase activity and β-catenin nuclear localization.

## 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.