Linked Life Data

20331634

Source:http://linkedlifedata.com/resource/pubmed/id/20331634

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-6-10
pubmed:abstractText
Bone marrow (BM) neovascularization and vascular endothelial growth factor (VEGF) expression in multiple myeloma (MM) correlate with disease progression. Brain derived neurotrophic factor (BDNF) is highly expressed by malignant plasma cells isolated from the majority of MM patients. Recently, BDNF was identified as a potential proangiogenic factor for the promotion of endothelial cell survival, induction of neoangiogenesis in ischemic tissues, and increase of VEGF expression in neuroblastoma. Since tropomyosin receptor kinase B (TrkB), the receptor of BDNF, is expressed by stromal cells within the BM milieu, here we sought to evaluate the involvement of BDNF/TrkB in myeloma-marrow stroma interaction and its effects on BM angiogenesis. TrkB was abundantly expressed by bone marrow stromal cells (BMSCs) isolated from healthy donors. Stimulation of BMSCs with BDNF induced a time- and dose- dependent increase in VEGF secretion, which was completely abolished by K252alpha, an inhibitor of TrkB. BDNF triggered activation of signal transducer and activator of transcription 3 (STAT3) and activator protein-1 (AP-1), whereas STAT3 was involved in mediating VEGF expression. We further delineated the biological significance of BDNF in MM by using lentiviral short-interfering RNA (shRNA). When myeloma cells were cocultured with BMSCs in a noncontact Transwell system, VEGF levels in supernatants were significantly decreased when BDNF expression was knocked down. Furthermore, silencing of BDNF expression significantly inhibited xenograft tumor growth and angiogenesis, and prolonged survival in mouse model. Our studies demonstrate that BDNF, as a potential stimulator of angiogenesis, contributes to MM tumorgenesis; it mediates stromal-MM cell interactions via selective activation of specific receptor TrkB and downstream signal transducer STAT3, regulating VEGF secretion.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1349-7006
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1117-24
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Lentiviral shRNA silencing of BDNF inhibits in vivo multiple myeloma growth and angiogenesis via down-regulated stroma-derived VEGF expression in the bone marrow milieu.
pubmed:affiliation
Institute of Hematology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't