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S100A4 released from highly bone-metastatic breast cancer cells plays a critical role in osteolysis

Bone Research 2019年第4期7卷 424-436页

作者： Haemin Kim Bongjun Kim Sang Il Kim Hyung Joon Kim brian yryu Junho Chung Zang Hee Lee Hong-Hee Kim Department of Cell and Developmental Biology BK21 Program and DRISeoul National UniversitySeoulKorea Department of Biochemistry and Molecular Biology Seoul National University College of MedicineSeoulKorea Cancer Research Institute Seoul National University College of MedicineSeoulKorea Department of Cancer Biology Seoul National University College of MedicineSeoulKorea Department of Oral Physiology BK21 PLUS Projectand Dental and Life Science InstituteSchool of DentistryPusan National UniversityYangsanKorea Interdisciplinary Program in Bioinformatics Seoul National University College of Natural SciencesSeoulKorea Department of Biomedical Sciences Seoul National University Graduate SchoolSeoulKorea

Bone destruction induced by breast cancer metastasis causes severe complications,including death,in breast cancer *** between cancer cells and skeletal cells in metastatic bone microenvironments is a principal element that drives tumor progression and ***-derived factors play fundamental roles in this form of *** identify soluble factors released from cancer cells in bone metastasis,we established a highly bone-metastatic subline of MDA-MB-231 breast cancer *** subline(mtMDA)showed a markedly elevated ability to secrete S100A4 protein,which directly stimulated osteoclast formation via surface receptor *** S100A4 stimulated osteoclastogenesis in vitro and bone loss in *** medium from mtMDA cells in which S100A4 was knocked down had a reduced ability to stimulate ***,the S100A4 knockdown cells elicited less bone destruction in mice than the control knockdown *** addition,administration of an anti-S100A4 monoclonal antibody(mAb)that we developed attenuated the stimulation of osteoclastogenesis and bone loss by mtMDA in *** together,our results suggest that S100A4 released from breast cancer cells is an important player in the osteolysis caused by breast cancer bone metastasis.

关键词： S100A4 breast metastatic

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