S100A4 released from highly bone-metastatic breast cancer cells plays a critical role in osteolysis
| Autor: | Hyung Joon Kim, Haemin Kim, Junho Chung, Zang Hee Lee, Bongjun Kim, Hong-Hee Kim, Sang Il Kim, Brian Y. Ryu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Histology Osteolysis Physiology Endocrinology Diabetes and Metabolism Article lcsh:Physiology 03 medical and health sciences 0302 clinical medicine Breast cancer Osteoclast Bone cancer Homeostasis Medicine lcsh:QH301-705.5 lcsh:QP1-981 business.industry Bone metastasis medicine.disease Metastatic breast cancer 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) Tumor progression 030220 oncology & carcinogenesis Cancer cell Cancer research business |
| Zdroj: | Bone Research, Vol 7, Iss 1, Pp 1-13 (2019) Bone Research |
| ISSN: | 2095-6231 |
| Popis: | Bone destruction induced by breast cancer metastasis causes severe complications, including death, in breast cancer patients. Communication between cancer cells and skeletal cells in metastatic bone microenvironments is a principal element that drives tumor progression and osteolysis. Tumor-derived factors play fundamental roles in this form of communication. To identify soluble factors released from cancer cells in bone metastasis, we established a highly bone-metastatic subline of MDA-MB-231 breast cancer cells. This subline (mtMDA) showed a markedly elevated ability to secrete S100A4 protein, which directly stimulated osteoclast formation via surface receptor RAGE. Recombinant S100A4 stimulated osteoclastogenesis in vitro and bone loss in vivo. Conditioned medium from mtMDA cells in which S100A4 was knocked down had a reduced ability to stimulate osteoclasts. Furthermore, the S100A4 knockdown cells elicited less bone destruction in mice than the control knockdown cells. In addition, administration of an anti-S100A4 monoclonal antibody (mAb) that we developed attenuated the stimulation of osteoclastogenesis and bone loss by mtMDA in mice. Taken together, our results suggest that S100A4 released from breast cancer cells is an important player in the osteolysis caused by breast cancer bone metastasis. |
| Databáze: | OpenAIRE |
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