Suppression of osteosarcoma progression by engineered lymphocyte-derived proteomes  

作　　者：Kexin Li Xun Sun Hudie Li Hailan Ma Meng Zhou Kazumasa Minami Keisuke Tamari Kazuhiko Ogawa Pankita HPandya MReza Saadatzadeh Melissa AKacena Karen EPollok Bai-Yan Li Hiroki Yokota 

机构地区：[1]Department of Pharmacology,School of Pharmacy,Harbin Medical University,Harbin,Heilongjiang 150081,China [2]Department of Biomedical Engineering,Indiana University Purdue University Indianapolis,Indianapolis,IN 46202,USA [3]Department of Radiation Oncology,Osaka University Graduate School of Medicine,Suita,Osaka 565-0871,Japan [4]Simon Comprehensive Cancer Center,Indiana University School of Medicine,Indianapolis,IN 46202,USA [5]Department of Pediatrics,Indiana University School of Medicine,Indianapolis,IN 46202,USA [6]Department of Orthopaedic Surgery,Indiana University School of Medicine,Indianapolis,IN 46202,USA [7]Indiana Center for Musculoskeletal Health,Indiana University School of Medicine,Indianapolis,IN 46202,USA

出　　处：《Genes & Diseases》2023年第4期1641-1656,共16页基因与疾病（英文）

基　　金：supported by The Biomechanics and Bio-materials Research Center at Indiana University-Purdue University Indianapolis,USA(No.2201-01);The NIH/Eunice Kennedy Shriver NICHD,USA(No.P50HD090215);The NIH/NCI Cancer Center Support Grant,USA(No.P30CA082709);The Tyler Trent Cancer Research Endowment for the Riley Hospital for Children IU-Health,USA;The Indiana University Grand ChallengeePrecision Health Initiative,USA.

摘　　要：Cancer cells tend to develop resistance to chemotherapy and enhance aggressive-ness.A counterintuitive approach is to tame aggressiveness by an agent that acts opposite to chemotherapeutic agents.Based on this strategy,induced tumor-suppressing cells(iTSCs)have been generated from tumor cells and mesenchymal stem cells.Here,we examined the possi-bility of generating iTSCs from lymphocytes by activating PKA signaling for suppressing the pro-gression of osteosarcoma(OS).While lymphocyte-derived CM did not present anti-tumor capabilities,the activation of PKA converted them into iTSCs.Inhibiting PKA conversely gener-ated tumor-promotive secretomes.In a mouse model,PKA-activated CM suppressed tumorinduced bone destruction.Proteomics analysis revealed that moesin(MSN)and calreticulin(Calr),which are highly expressed intracellular proteins in many cancers,were enriched in PKA-activated CM,and they acted as extracellular tumor suppressors through CD44,CD47,and CD91.The study presented a unique option for cancer treatment by generating iTSCs that secret tumor-suppressive proteins such as MSN and Calr.We envision that identifying these tu-mor suppressors and predicting their binding partners such as CD44,which is an FDA-approved oncogenic target to be inhibited,may contribute to developing targeted protein therapy.

关 键 词：CALRETICULIN LYMPHOCYTES MOESIN OSTEOSARCOMA PKA Proteome 

分 类 号：R73[医药卫生—肿瘤]