Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0026764 (
multiple myeloma
)
36,148
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID: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). 1805 85
Multiple myeloma
is characterized by slowly growing clones of malignant plasma cells in the bone marrow. The malignant state is frequently accompanied by osteolytic bone disease due to a
disturbed balance
between osteoblasts and osteoclasts. Bone morphogenetic proteins (BMPs) are present in the bone marrow and are important for several aspects of
myeloma
pathogenesis including growth and survival of tumor cells, bone homeostasis, and anemia. Among cancer cells,
myeloma
cells are particularly sensitive to growth inhibition and apoptosis induced by BMPs and therefore represent good models to study BMP receptor usage and signaling. Our review highlights and discusses the current knowledge on BMP signaling in
myeloma
.
...
PMID:The role of bone morphogenetic proteins in myeloma cell survival. 2485 40
