Department of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin, China; Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, United States
Department of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin, China; Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, United States
Nathan H Dimmitt
Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, United States
Guofan Qu
Department of Orthopedic Surgery, Harbin Medical University Cancer Hospital, Harbin, China
Junjie Bao
Department of Orthopedic Surgery, Harbin Medical University Cancer Hospital, Harbin, China
Pankita H Pandya
Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, United States; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, United States
M Reza Saadatzadeh
Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, United States; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, United States
Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, United States; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, United States; Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, United States
Karen E Pollok
Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, United States; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, United States
Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, United States; Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, United States
Bai-Yan Li
Department of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin, China
Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, United States; Indiana University Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, United States; Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, United States
Osteosarcoma (OS) is the common primary bone cancer that affects mostly children and young adults. To augment the standard-of-care chemotherapy, we examined the possibility of protein-based therapy using mesenchymal stem cells (MSCs)-derived proteomes and OS-elevated proteins. While a conditioned medium (CM), collected from MSCs, did not present tumor-suppressing ability, the activation of PKA converted MSCs into induced tumor-suppressing cells (iTSCs). In a mouse model, the direct and hydrogel-assisted administration of CM inhibited tumor-induced bone destruction, and its effect was additive with cisplatin. CM was enriched with proteins such as calreticulin, which acted as an extracellular tumor suppressor by interacting with CD47. Notably, the level of CALR transcripts was elevated in OS tissues, together with other tumor-suppressing proteins, including histone H4, and PCOLCE. PCOLCE acted as an extracellular tumor-suppressing protein by interacting with amyloid precursor protein, a prognostic OS marker with poor survival. The results supported the possibility of employing a paradoxical strategy of utilizing OS transcriptomes for the treatment of OS.
