Linked Life Data

18703490

Source:http://linkedlifedata.com/resource/pubmed/id/18703490

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2008-8-15
pubmed:abstractText
The expression of the chemokine CC-chemokine ligand 20 (CCL20)/macrophage inflammatory protein (MIP)-3alpha and its receptor CC-chemokine receptor 6 (CCR6) by multiple myeloma (MM) and microenvironment cells and their potential relationship with osteoclast (OC) formation and osteolytic bone lesions in MM patients was investigated in this study. First, we found that MM cells rarely produce CCL20/MIP-3alpha but up-regulate its production by bone marrow (BM) osteoprogenitor cells and osteoblasts in coculture with the involvement of soluble factors as interleukin-1beta and tumor necrosis factor alpha. MM cells also stimulate both CCL20/MIP-3alpha and CCR6 expression by OCs in coculture. Thereafter, we showed that CCL20/MIP-3alpha significantly increases both the number of multinucleated tartrate-resistant acid phosphatase-positive OCs and receptor activator of nuclear factor-kappaB-positive OC progenitor cells similar to CCL3/MIP-1alpha. Finally, we found that blocking anti-CCL20/MIP-3alpha and anti-CCR6 antibodies significantly inhibits MM-induced OC formation. In vitro data were further expanded in vivo analyzing a total number of 64 MM patients. Significantly higher CCL20/MIP-3alpha levels were detected in MM patients versus monoclonal gammopathy of uncertain significance (MGUS) subjects and in MM osteolytic patients versus nonosteolytic ones. Moreover, a significant increase of CCL20/MIP-3alpha-positive osteoblasts in osteolytic MM patients compared with nonosteolytic ones was observed. Interestingly, no significant difference in BM CCL20/MIP-3alpha expression and level was observed between MGUS and nonosteolytic MM patients. Our data indicate that CCL20/MIP-3alpha and its receptor CCR6 are up-regulated in the bone microenvironment by MM cells and contribute to OC formation and osteolytic bone lesions in MM patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
68
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6840-50
pubmed:dateRevised
2011-6-13
pubmed:meshHeading
pubmed-meshheading:18703490-Bone Diseases, pubmed-meshheading:18703490-Chemokine CCL20, pubmed-meshheading:18703490-Coculture Techniques, pubmed-meshheading:18703490-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:18703490-Fluorescent Antibody Technique, pubmed-meshheading:18703490-Humans, pubmed-meshheading:18703490-Immunoenzyme Techniques, pubmed-meshheading:18703490-Multiple Myeloma, pubmed-meshheading:18703490-Osteoblasts, pubmed-meshheading:18703490-Osteoclasts, pubmed-meshheading:18703490-Osteogenesis, pubmed-meshheading:18703490-Paraproteinemias, pubmed-meshheading:18703490-RNA, Messenger, pubmed-meshheading:18703490-Receptors, CCR6, pubmed-meshheading:18703490-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:18703490-Stem Cells, pubmed-meshheading:18703490-Tumor Cells, Cultured
pubmed:year
2008
pubmed:articleTitle
CC-chemokine ligand 20/macrophage inflammatory protein-3? and CC-chemokine receptor 6 are overexpressed in myeloma microenvironment related to osteolytic bone lesions.
pubmed:affiliation
Hematology and Bone Marrow Transplantation Center, University of Parma, Parma, Italy. Nicola.Giuliani@unipr.it
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't