Integrated proteomic profiling identifies amino acids selectively cytotoxic to pancreatic cancer cells  

作　　者：Alfred Akinlalu Zachariah Flaten Komila Rasuleva Md Saimon Mia Aaron Bauer Santhalingam Elamurugan Nega Ejjigu Sudipa Maity Amara Arshad Min Wu Wenjie Xia Jia Fan Ang Guo Sijo Mathew Dali Sun 

机构地区：[1]Department of Electrical and Computer Engineering,University of Denver,2155 E Wesley Avenue,Denver,CO 80210,USA [2]Biomedical Engineering Program,North Dakota State University,1401 Centennial Boulevard,Engineering Administration,Room 203,Fargo,ND 58102,USA [3]Department of Pharmaceutical Sciences,School of Pharmacy,North Dakota State University,1001 S.1401 Albrecht Boulevard Sudro Hall,Fargo,ND 58102,USA [4]Materials and Nanotechnology Program,North Dakota State University,1410 North 14th Avenue,CIE 201,Fargo,ND 58102,USA [5]Wenzhou Institute,University of Chinese Academy of Sciences,Wenzhou,Zhejiang 325000,China [6]Department of Aerospace Engineering,Iowa State University,Ames,IA 50011,USA [7]Center for Cellular and Molecular Diagnostics,Tulane University School of Medicine,1430 Tulane Avenue,New Orleans,LA 70112,USA [8]Department of Biochemistry and Molecular Biology,Tulane University School of Medicine,1430 Tulane Avenue,New Orleans,LA 70112,USA [9]Knoebel Institute for Healthy Aging,University of Denver,2155 E Wesley Avenue,Denver,CO 80210,USA

出　　处：《The Innovation》2024年第3期138-145,共8页创新（英文）

基　　金：The authors acknowledge North Dakota State University Center for Computationally Assisted Science and Technology for computing resources.This work was financially supported by grants from the National Cancer Institute(R21CA270748,R03CA252783)and the National Institute of General Medical Sciences(U54GM128729)of National Institutes of Health to D.S.,NDSU EPSCoR STEM Research and Education fund(FAR0032086)to D.S.,ND EPSCoR:Advancing Science Excellence in ND(FAR0030554)to D.S.,and National Science Foundation(NSF)under NSF EPSCoR Track-1 Cooperative Agreement(OIA no.1355466)to D.S.,the National Institue of General Medical Sciences(P20GM109036)to J.F.,NSF under NSF OIA ND-ACES(award no.1946202)to W.X.,and NDSU Foundation and Alumni Association to D.S.

摘　　要：Pancreatic adenocarcinoma(PDAC)is one of the most deadly cancers,characterized by extremely limited therapeutic options and a poor prognosis,as it is often diagnosed during late disease stages.Innovative and selective treatments are urgently needed,since current therapies have limited efficacy and significant side effects.Through proteomics analysis of extracellular vesicles,we discovered an imbalanced distribution of amino acids secreted by PDAC tumor cells.Our findings revealed that PDAC cells preferentially excrete proteins with certain preferential amino acids,including isoleucine and histidine,via extracellular vesicles.These amino acids are associated with disease progression and can be targeted to elicit selective toxicity to PDAC tumor cells.Both in vitro and in vivo experiments demonstrated that supplementation with these specific amino acids effectively eradicated PDAC cells.Mechanistically,we also identified XRN1 as a potential target for these amino acids.The high selectivity of this treatment method allows for specific targeting of tumor metabolism with very low toxicity to normal tissues.Furthermore,we found this treatment approach is easy-to-administer and with sustained tumor-killing effects.Together,our findings reveal that exocytosed amino acids may serve as therapeutic targets for designing treatments of intractable PDAC and potentially offer alternative treatments for other types of cancers.

关 键 词：finding identif SELECTIVITY 

分 类 号：R735.9[医药卫生—肿瘤]