PMID- 16959214
OWN - NLM
STAT- MEDLINE
DCOM- 20061107
LR  - 20211203
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 349
IP  - 3
DP  - 2006 Oct 27
TI  - Malignant hematopoietic cells induce an increased expression of VEGFR-1 and 
      VEGFR-3 on bone marrow endothelial cells via AKT and mTOR signalling pathways.
PG  - 1003-10
AB  - Angiogenesis plays a significant role in a variety of malignant hematologic 
      diseases, and it is recognized that it has prognostic value. However, the 
      cellular mechanisms by which malignant hematologic cells induce angiogenesis are 
      not well understood. In order to investigate the role of cells from B-cell 
      chronic lymphocytic leukemia (B-CLL) and multiple myeloma (MM) in angiogenesis on 
      human bone marrow endothelial cells (HBMEC), we analyzed the impact of factors 
      secreted by B-CLL cells and by MM cells on HBMEC capillary tube formation on 
      matrigel. It was found that, in addition to the secretion of angiogenic factors 
      VEGF and b-FGF by B-CLL and MM cells, MM cells (but not B-CLL cells) induced a 
      dramatic increase in expression of VEGFR-1 and VEGFR-3 on human bone marrow 
      endothelial cells (HBMEC). It would seem that this increase in VEGFR-3 occurred 
      via the ERK and mTOR pathways, since their respective inhibitors U0126, LY294002 
      or rapamycin were responsible for a decrease of VEGFR-3. In response to MM 
      cells-increased VEGF receptors on HBMEC, endothelial cell migration was enhanced 
      in a wound artificially produced in a semi-confluent HBMEC culture, a phenomenon 
      which was also down-regulated by the same inhibitors that reversed the increase 
      in VEGF receptors. The present study suggests that, in addition to the classic 
      angiogenic pathway, another mechanism related to an increased expression of 
      VEGFRs on HBMEC might exist in malignant hematopoietic angiogenesis.
FAU - Mirshahi, P
AU  - Mirshahi P
AD  - INSERM, UMR736, IFR 58, Universite Pierre et Marie Curie, 75006 Paris, France.
FAU - Toprak, S K
AU  - Toprak SK
FAU - Faussat, A M
AU  - Faussat AM
FAU - Dubrulle, S
AU  - Dubrulle S
FAU - Marie, J P
AU  - Marie JP
FAU - Soria, C
AU  - Soria C
FAU - Soria, J
AU  - Soria J
FAU - Mirshahi, M
AU  - Mirshahi M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060830
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Culture Media)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-3)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Bone Marrow Cells/*metabolism
MH  - Culture Media
MH  - Endothelial Cells/metabolism/pathology
MH  - Fibroblast Growth Factor 2/metabolism
MH  - Humans
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*metabolism/pathology
MH  - Multiple Myeloma/blood supply/*metabolism
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Protein Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases
MH  - Tumor Cells, Cultured
MH  - Vascular Endothelial Growth Factor A/metabolism
MH  - Vascular Endothelial Growth Factor Receptor-1/*metabolism
MH  - Vascular Endothelial Growth Factor Receptor-3/antagonists & 
      inhibitors/*metabolism
EDAT- 2006/09/09 09:00
MHDA- 2006/11/09 09:00
CRDT- 2006/09/09 09:00
PHST- 2006/08/18 00:00 [received]
PHST- 2006/08/21 00:00 [accepted]
PHST- 2006/09/09 09:00 [pubmed]
PHST- 2006/11/09 09:00 [medline]
PHST- 2006/09/09 09:00 [entrez]
AID - S0006-291X(06)01941-3 [pii]
AID - 10.1016/j.bbrc.2006.08.132 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2006 Oct 27;349(3):1003-10. doi: 
      10.1016/j.bbrc.2006.08.132. Epub 2006 Aug 30.