Linked Life Data

18053985

Source:http://linkedlifedata.com/resource/pubmed/id/18053985

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-2-25
pubmed:abstractText
Bone destruction is one of the most debilitating manifestations of multiple myeloma (MM) and results from the interaction of myeloma cells with the bone marrow microenvironment. Within the bone marrow, the disturbed balance between osteoclasts and osteoblasts is important for the development of lytic lesions. However, the mechanisms behind myeloma-mediated bone destruction are not completely understood. In order to address the importance of myeloma cell-osteoclast interactions in MM pathogenesis, we have developed a functional coculture system. We found that myeloma-osteoclast interactions resulted in stimulation of myeloma cell growth and osteoclastic activity through activation of major signalling pathways and upregulation of proteases. Signals from osteoclasts activated the p44/p42 MAPK, STAT3 and PI3K/Akt pathways in myeloma cells. In turn, myeloma cells triggered p38 MAPK and NF-kappaB signalling in osteoclasts. Myeloma-osteoclast interactions stimulated the production of TRAP, cathepsin K, matrix metalloproteinase (MMP)-1, -9, and urokinase plasminogen activator (uPA). Consistent data with myeloma cell lines and primary myeloma cells underlined the biological relevance of these findings. In conclusion, we demonstrated the critical role of myeloma cell-osteoclast interactions in the existing interdependence between tumour expansion and bone disease. The identified molecular events might provide the rationale for novel treatment strategies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0014-4827
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
314
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1082-93
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18053985-Acid Phosphatase, pubmed-meshheading:18053985-Bone Resorption, pubmed-meshheading:18053985-Cathepsin K, pubmed-meshheading:18053985-Cathepsins, pubmed-meshheading:18053985-Cell Communication, pubmed-meshheading:18053985-Cell Line, Tumor, pubmed-meshheading:18053985-Cell Proliferation, pubmed-meshheading:18053985-Coculture Techniques, pubmed-meshheading:18053985-Gene Expression Regulation, Neoplastic, pubmed-meshheading:18053985-Humans, pubmed-meshheading:18053985-Isoenzymes, pubmed-meshheading:18053985-Matrix Metalloproteinases, pubmed-meshheading:18053985-Multiple Myeloma, pubmed-meshheading:18053985-Osteoclasts, pubmed-meshheading:18053985-Signal Transduction, pubmed-meshheading:18053985-Tumor Cells, Cultured, pubmed-meshheading:18053985-Up-Regulation, pubmed-meshheading:18053985-Urokinase-Type Plasminogen Activator
pubmed:year
2008
pubmed:articleTitle
Interactions of myeloma cells with osteoclasts promote tumour expansion and bone degradation through activation of a complex signalling network and upregulation of cathepsin K, matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA).
pubmed:affiliation
Department of Haematology and Oncology, Charité Universitaetsmedizin Berlin, Charitéplatz 1, Berlin, Germany. m.hecht@hameln-rds.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't