IGFBP-3 promotes cachexia-associated lipid loss by suppressing insulin-like growth factor/insulin signaling

作     者：Xiaohui Wang Jia Li Wei Zhang Feng Wang Yunzi Wu Yulin Guo Dong Wang Xinfeng Yu Ang Li Fei Li Yibin Xie 

作者机构：Department of General SurgeryXuanwu HospitalCapital Medical UniversityBeijing 100053China Department of Gastrointestinal SurgeryBeijing Tsinghua Changgung HospitalSchool of Clinical MedicineTsinghua UniversityBeijing 102218China Department of Pancreatic and Gastric SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of PharmacologySchool of Basic Medical SciencesCapital Medical UniversityBeijing 100069China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2023年第136卷第8期

页      面：974-985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：National Natural Science Foundation of China(No.82073876) Beijing Natural Science Foundation(No.7202012) 

主　　题：Biomarker Cancer Cachexia Insulin-like growth factor binding protein-3 Lipid loss 

摘      要：Background:Progressive lipid loss of adipose tissue is a major feature of cancer-associated *** addition to systemic immune/inflammatory effects in response to tumor progression,tumor-secreted cachectic ligands also play essential roles in tumor-induced lipid ***,the mechanisms of tumor-adipose tissue interaction in lipid homeostasis are not fully ***:The yki-gut tumors were induced in fruit *** metabolic assays were performed to investigate the lipolysis level of different types of insulin-like growth factor binding protein-3(IGFBP-3)treated *** was used to display phenotypes of tumor cells and *** polymerase chain reaction(qPCR)analysis was carried out to examine the gene expression levels such as Acc1,Acly,and Fasn et ***:In this study,it was revealed that tumor-derived IGFBP-3 was an important ligand directly causing lipid loss in matured ***-3,which is highly expressed in cachectic tumor cells,antagonized insulin/IGF-like signaling(IIS)and impaired the balance between lipolysis and lipogenesis in 3T3-L1 *** medium from cachectic tumor cells,such as Capan-1 and C26 cells,contained excessive IGFBP-3 that potently induced lipolysis in ***,neutralization of IGFBP-3 by neutralizing antibody in the conditioned medium of cachectic tumor cells significantly alleviated the lipolytic effect and restored lipid storage in ***,cachectic tumor cells were resistant to IGFBP-3 inhibition of IIS,ensuring their escape from IGFBP-3-associated growth ***,cachectic tumor-derived ImpL2,the IGFBP-3 homolog,also impaired lipid homeostasis of host cells in an established cancer-cachexia model in *** importantly,IGFBP-3 was highly expressed in cancer tissues in pancreatic and colorectal cancer patients,especially higher in the sera of cachectic cancer patients than non-cachexia cancer ***:Our stu