Adipocyte-derived SFRP5 inhibits breast cancer cells migration and invasion through Wnt and epithelial-mesenchymal transition signaling pathways

查看全文 作　　者：Wenzhong [1,2]Zhou;Chunmiao [1,2]Ye;Liang [2,3]Li;Liyuan [2,3]Liu;Fei [2,3]Wang;Lixiang [2,3]Yu;Fei [2,3]Zhou;Yujuan [2,3]Xiang;Yongjiu [2,3]Wang;Gengshen [1,2]Yin;Zhongbing [2,3]Ma;Qinye [2,3]Fu;Qiang [2,3]Zhang;Dezong [2,3]Gao;Shuya [2,3]Huang;Zhigang [2,3]Yu

机构地区：[1]School of Medicine,Cheeloo College of Medicine,Shandong University,Jinan 250012,China;[2]Department of Breast Surgery,the Second Hospital,Cheeloo College of Medicine,Shandong University,Jinan 250033,China;[3]Institute of Translational Medicine of Breast Disease Prevention and Treatment,Shandong University,Jinan 250033,China

出　　处：《Chinese Journal of Cancer Research》索引2020年第32卷第3期,共14页

基　　金：the Major Scientific and Technological Innovation Project of Shandong Province(No.2017CXGC1212);National Natural Science Foundation of China(No.31701258);the National Key Research and Development Program of China(No.2016YFC0901300)。 摘　　要：Objective:Obesity is closely associated with metastasis in breast cancer patients.Secreted frizzled-related protein 5(SFRP5),one of the novel adipokines with anti-inflammatory properties,is associated with obesity.This study aims to study the role of SFRP5 in the crosstalk between obesity and breast cancer metastasis and identify the underlying mechanism.Methods:3T3-L1 pre-adipocytes were differentiated to mature adipocytes and a hypertrophic adipocyte model was induced with palmitic acid(PA).Cell motility was measured in MDA-MB-231 and MCF-7 breast cancer cells co-cultured with adipocytes conditioned medium(CM)with or without SFRP5 protein.Wnt and epithelialmesenchymal transition(EMT)signal pathways were investigated by western blot.Circulating SFRP5 level in 218 breast cancer patients and the association with clinicopathologic characteristics of breast cancer were further determined.Online databases ENCORI and PREDICT Plus were used to exam the link between SFRP5 and prognosis.Results:Reduced SFRP5 level was detected in the hypertrophic adipocyte model.Recombinant SFRP5 protein inhibited MDA-MB-231 and MCF-7 cells invasion and migration induced by PA-treated adipocyte CM,and SFRP5 inhibition by specific antibody reversed the effect of SFRP5.Furthermore,SFRP5 significantly inhibited Wnt and downstream EMT in breast cancer cells.Low circulating SFRP5 level correlated with body mass index(BMI),lymph node(LN)metastasis,TNM stage and high Ki67 expression in breast cancer patients.Increased SFRP5 level was associated with favorable predicted survival.Kaplan-Meier curves showed high SFRP5 level in tumor tissue was associated with better outcome of breast cancer patients.Conclusions:Our findings demonstrated SFRP5 is a vital adipokine that mediates the crosslink between obesity and the metastatic potential of breast cancer.Promotion of SFRP5 expression in the adipose microenvironment may represent a novel approach for preventing breast cancer metastasis. 关键词：OBESITY ADIPOCYTES breast cancer metastasis SFRP5 EMT

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Adipocyte-derived SFRP5 inhibits breast cancer cells migration and invasion through Wnt and epithelial-mesenchymal transition signaling pathways

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