Induced Tumor-Suppressing (iTS) Cell-Based Approach for Protecting the Bone from Advanced Prostate Cancer
Year: 2026
Type: article
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.
Source: Biomolecules
DOI: 10.3390/biom16020240
Institutions: Capital Medical University, Purdue University in Indianapolis, Indiana University – Purdue University Indianapolis, Harbin Medical University, The University of Osaka, Purdue University West Lafayette, Oklahoma State University, Indiana University Indianapolis, Indiana University School of Medicine, Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,258
OpenAlex ID: W7127377277