Overexpression of Lrp5 enhanced the anti-breast cancer effects of osteocytes in bone

作     者：Shengzhi Liu Di Wu Xun Sun Yao Fan Rongrong Zha Aydin Jalali Yan Feng Kexin Li Tomohiko Sano Nicole Vike Fangjia Li Joseph Rispoli Akihiro Sudo Jing Liu Alexander Robling Harikrishna Nakshatri Bai-Yan Li Hiroki Yokota Shengzhi Liu;Di Wu;Xun Sun;Yao Fan;Rongrong Zha;Aydin Jalali;Yan Feng;Kexin Li;Tomohiko Sano;Nicole Vike;Fangjia Li;Joseph Rispoli;Akihiro Sudo;Jing Liu;Alexander Robling;Harikrishna Nakshatri;Bai-Yan Li;Hiroki Yokota

作者机构：Department of Biomedical EngineeringIndiana University Purdue University IndianapolisIndianapolisINUSA Department of PharmacologySchool of PharmacyHarbin Medical UniversityHarbinChina Department of PharmacyThe Second Affiliated Hospital of Dalian Medical UniversityDalianChina Department of Orthopedic SurgeryMie UniversityTsuMieJapan Weldon School of Biomedical EngineeringPurdue UniversityWest LafayetteINUSA Department of PhysicsIndiana University Purdue University IndianapolisIndianapolisINUSA Department of Anatomy and Cell BiologyIndiana University School of MedicineIndianapolisINUSA Indiana Center for Musculoskeletal HealthIndiana University School of MedicineIndianapolisINUSA Department of SurgeryIndiana University School of MedicineIndianapolisINUSA Simon Cancer CenterIndiana University School of MedicineIndianapolisINUSA 

出 版 物：《Bone Research》 (骨研究（英文版）)

年 卷 期：2021年第9卷第4期

页      面：494-506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：This study was supported in part by funds from a breast cancer advocacy group,100 Voices of Hope(H.Y.) the Indiana University Precision Health Initiative(H.N.) NIH R01AR52144(H.Y.),R03CA238555(H.Y.),and R01AR053237(A.R.) 

主　　题：cytes elevated inhibited 

摘      要：Osteocytes are the most abundant cells in bone,which is a frequent site of breast cancer ***,we focused on Wnt signaling and evaluated tumor-osteocyte *** animal experiments,mammary tumor cells were inoculated into the mammary fat pad and *** role of Lrp5-mediated Wnt signaling was examined by overexpressing and silencing Lrp5 in osteocytes and establishing a conditional knockout mouse *** results revealed that administration of osteocytes or their conditioned medium(CM)inhibited tumor progression and *** overexpressing Lrp5 or β-catenin displayed strikingly elevated tumor-suppressive activity,accompanied by downregulation of tumor-promoting chemokines and upregulation of apoptosis-inducing and tumor-suppressing proteins such as *** antitumor effect was also observed with osteocyte-derived CM that was pretreated with a Wnt-activating ***,silencing Lrp5 in tumors inhibited tumor progression,while silencing Lrp5 in osteocytes in conditional knockout mice promoted tumor *** exhibited elevated Lrp5 expression in response to tumor cells,implying that osteocytes protect bone through canonical Wnt ***,our results suggest that the Lrp5/β-catenin axis activates tumor-promoting signaling in tumor cells but tumor-suppressive signaling in *** envision that osteocytes with Wnt activation potentially offer a novel cell-based therapy for breast cancer and osteolytic bone metastasis.