PMID- 19724912
OWN - NLM
STAT- MEDLINE
DCOM- 20091211
LR  - 20190606
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 35
IP  - 4
DP  - 2009 Oct
TI  - Oligosaccharides of hyaluronan induce angiogenesis through distinct CD44 and 
      RHAMM-mediated signalling pathways involving Cdc2 and gamma-adducin.
PG  - 761-73
AB  - We used short-interfering RNA (siRNA) to knockdown the hyaluronan (HA) receptors 
      CD44 and the receptor for hyaluronan-mediated motility (RHAMM) in vascular 
      endothelial cells to investigate their role in angiogenesis. We showed that CD44 
      and RHAMM single knockdown inhibited low molecular weight hyaluronan 
      (o-HA)-induced endothelial cell tube formation in Matrigel, but no change in the 
      control, epidermal growth factor-induced tube formation was observed. Using a 
      Kinexus phosphoprotein array and confirmational Western blotting we were able to 
      show a differential effect on HA-induced protein expression after CD44 and RHAMM 
      knockdown. CD44 knockdown abolished o-HA-induced membrane phospho-protein kinase 
      C-alpha (PKC-alpha) and down-stream phospho-gamma-adducin expression. Using the 
      PKC inhibitor Go6976, we demonstrated the involvement of PKC-alpha and 
      gamma-adducin in o-HA-induced tube formation, whilst o-HA-induced enzymatic 
      activity of MMP9 was also reduced. This suggests that endothelial tube formation 
      involves activation of MMP9 via PKC-alpha. Furthermore, the involvement of 
      gamma-adducin in o-HA-induced F-actin cytoskeleton rearrangement was 
      CD44-dependent and the reduction of CD44 expression lead to a change in 
      endothelial cell morphology. Both RHAMM and CD44 knockdown completely inhibited 
      o-HA-induced Cdc2 (Cdk1) phosphorylation suggesting a possible involvement in 
      cell cycle control. Although CD44 and RHAMM are both involved in o-HA-induced 
      endothelial tube formation in Matrigel, they mediate distinct angiogenic 
      signalling pathway and for the first time we demonstrated the specific 
      involvement of gamma-adducin in CD44/o-HA-induced endothelial tube formation. The 
      data presented here extend our understanding of key stages of the processes of 
      o-HA-induced angiogenesis which may have relevance to tumour progression.
FAU - Matou-Nasri, S
AU  - Matou-Nasri S
AD  - School of Biology, Chemistry and Health Science, Manchester Metropolitan 
      University, Manchester M1 5GD, UK.
FAU - Gaffney, J
AU  - Gaffney J
FAU - Kumar, S
AU  - Kumar S
FAU - Slevin, M
AU  - Slevin M
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Actins)
RN  - 0 (Calmodulin-Binding Proteins)
RN  - 0 (Carbazoles)
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (Oligosaccharides)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (adducin)
RN  - 0 (hyaluronan-mediated motility receptor)
RN  - 136194-77-9 (Go 6976)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - 9004-61-9 (Hyaluronic Acid)
RN  - EC 2.7.11.13 (Protein Kinase C-alpha)
RN  - EC 2.7.11.22 (CDC2 Protein Kinase)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Actins/metabolism
MH  - Animals
MH  - Blotting, Western
MH  - CDC2 Protein Kinase/*metabolism
MH  - Calmodulin-Binding Proteins/*metabolism
MH  - Carbazoles/pharmacology
MH  - Cattle
MH  - Cell Shape/drug effects
MH  - Cells, Cultured
MH  - Endothelial Cells/drug effects/immunology/*metabolism
MH  - Epidermal Growth Factor/metabolism
MH  - Extracellular Matrix Proteins/genetics/*metabolism
MH  - Fluorescent Antibody Technique
MH  - Hyaluronan Receptors/genetics/*metabolism
MH  - Hyaluronic Acid/analogs & derivatives/*metabolism
MH  - Matrix Metalloproteinase 9/metabolism
MH  - *Neovascularization, Physiologic/drug effects
MH  - Oligosaccharides/*metabolism
MH  - Phosphorylation
MH  - Protein Array Analysis
MH  - Protein Kinase C-alpha/antagonists & inhibitors/metabolism
MH  - Protein Kinase Inhibitors/pharmacology
MH  - RNA Interference
MH  - RNA, Small Interfering/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Signal Transduction/drug effects
EDAT- 2009/09/03 06:00
MHDA- 2009/12/16 06:00
CRDT- 2009/09/03 09:00
PHST- 2009/09/03 09:00 [entrez]
PHST- 2009/09/03 06:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
AID - 10.3892/ijo_00000389 [doi]
PST - ppublish
SO  - Int J Oncol. 2009 Oct;35(4):761-73. doi: 10.3892/ijo_00000389.