Tunable hybrid hydrogels with multicellular spheroids for modeling desmoplastic pancreatic cancer
作者机构：Terasaki Institute for Biomedical Innovation(TIBI)Los AngelesCA90024USA Department of Materials Science and EngineeringPohang University of Science and Technology(POSTECH)PohangGyeongbuk37673Republic of Korea College of PharmacyKangwon National UniversityChuncheonGangwon24341Republic of Korea Department of Materials Science and EngineeringKorea UniversitySeoul02841Republic of Korea Institute for Convergence Research and Education in Advanced TechnologyYonsei UniversityIncheon 21983Republic of Korea College of PharmacyKorea UniversitySejong30019Republic of Korea
出 版 物：《Bioactive Materials》 (生物活性材料（英文）)
年 卷 期：2023年第25卷第7期
页 面：360-373页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：Dr.M.Ermis and Dr.N.Falcone contributed equally to this work.The authors gratefully acknowledge the funding by the National Institutes of Health(HL140951,HL137193,CA257558,DK130566) Dr.M.Ermis acknowledges The Scientific and Technological Research Council of Turkiye for 2219-International Postdoctoral Research Fellowship Program
主 题：Pancreatic cancer Desmoplasia Fibrosis Extracellular matrix Tumor microenvironment
摘 要：The tumor microenvironment consists of diverse,complex etiological *** matrix component of pancreatic ductal adenocarcinoma(PDAC)plays an important role not only in physical properties such as tissue rigidity but also in cancer progression and therapeutic *** significant efforts have been made to model desmoplastic PDAC,existing models could not fully recapitulate the etiology to mimic and understand the progression of ***,two major components in desmoplastic pancreatic matrices,hyaluronic acid-and gelatin-based hydrogels,are engineered to provide matrices for tumor spheroids composed of PDAC and cancer-associated fibroblasts(CAF).Shape analysis profiles reveals that incorporating CAF contributes to a more compact tissue *** expression levels of markers associated with proliferation,epithelial to mesenchymal transition,mechanotransduction,and progression are observed for cancer-CAF spheroids cultured in hyper desmoplastic matrix-mimicking hydrogels,while the trend can be observed when those are cultured in desmoplastic matrix-mimicking hydrogels with the presence of transforming growth factor-β1(TGF-β1).The proposed multicellular pancreatic tumor model,in combination with proper mechanical properties and TGF-β1 supplement,makes strides in developing advanced pancreatic models for resembling and monitoring the progression of pancreatic tumors,which could be potentially applicable for realizing personalized medicine and drug testing applications.
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