Knockdown of Bone Morphogenetic Proteins Type 1a Receptor (BMPR1a) in Breast Cancer Cells Protects Bone from Breast Cancer-Induced Osteolysis by Suppressing RANKL Expression
| Autor: | Yang Liu, Zhong-Liang Deng, Dong-Dong Tian, Xiao Jiang, Wei Yuan, Ran-Xi Zhang, Hao Li, Hou-Qing Chen, Yang Wang |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Osteoclastogenesis Physiology Pyridines Osteolysis p38 Mitogen-Activated Protein Kinases lcsh:Physiology Mice Breast cancer Osteogenesis lcsh:QD415-436 Bone morphogenetic protein receptor lcsh:QP1-981 biology Chemistry Imidazoles Bone metastasis Bmpr1a medicine.anatomical_structure RANKL MCF-7 Cells Female RNA Interference Signal Transduction Down-Regulation Mice Nude Bone Marrow Cells Breast Neoplasms Bone morphogenetic protein Bone and Bones lcsh:Biochemistry 03 medical and health sciences Osteoclast Cell Line Tumor medicine Animals Humans Bone Morphogenetic Protein Receptors Type I Tibia Tumor-stromal interaction RANK Ligand medicine.disease 030104 developmental biology RAW 264.7 Cells Culture Media Conditioned Cancer cell biology.protein Cancer research Bone marrow |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 45, Iss 5, Pp 1759-1771 (2018) |
| ISSN: | 1421-9778 |
| Popis: | Background/Aims: Bone morphogenetic proteins (BMPs) and BMP receptors widely participate in osteolytic metastasis of breast cancer, while their role in tumor-stromal interaction is largely unknown. In this study, we investigated whether BMP receptor type 1a (BMPR1a) can alter the interaction between metastatic cancer cells and osteoclast precursors. Methods: Adenovirus-mediated RNA interference was used to interrupt target genes of human breast cancer cell lines and nude mice were injected intratibially with the cancer cells. Tumor-bearing mice were examined by bioluminescence imaging and microCT. Sections of metastatic legs were measured by a series of staining methods. Murine bone marrow mononuclear cells or RAW264.7 cells were cultured with conditioned media of breast cancer cells. RT-PCR, Western blotting and ELISA were used to test mRNA and protein expressions of target molecules. Results: Expression of BMPR1a of MDA-MB-231-luc cells at tumor-bone interface was apparently stronger than that of cancer cells distant from the interface. Mice injected with BMPR1a-knockdown MDA-MB-231-luc cells showed reduced tumor growth and bone destruction compared with control groups. Knockdown (KD) of BMPR1a of MDA-MB-231-luc cells or MCF-7 cells decreased the level of receptor activator for NF-κB ligand (RANKL). Level of RANKL in MDA-MB-231-luc cells or MCF-7 cells was reduced by p38 inhibitor. Compared with control group, knockdown of p38 of breast cancer cells decreased cancer-induced osteoclastogenesis. Conclusion: Knockdown of BMPR1a of breast cancer cells suppresses their production of RANKL via p38 pathway and inhibits cancer-induced osteoclastogenesis, which indicates that BMPR1a might be a possible target in breast cancer-induced osteolytic metastasis. |
| Databáze: | OpenAIRE |
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