PMID- 12183053
OWN - NLM
STAT- MEDLINE
DCOM- 20020923
LR  - 20190610
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1591
IP  - 1-3
DP  - 2002 Aug 19
TI  - CD44 stimulation by fragmented hyaluronic acid induces upregulation and tyrosine 
      phosphorylation of c-Met receptor protein in human chondrosarcoma cells.
PG  - 37-44
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) can induce proliferation and 
      motility and promote invasion of tumor cells. Since HGF/SF receptor, c-Met, is 
      expressed by tumor cells, and since stimulation of CD44, a transmembrane 
      glycoprotein known to bind hyaluronic acid (HA) in its extracellular domain, is 
      involved in activation of c-Met, we have studied the effects of CD44 stimulation 
      by ligation with HA upon the expression and tyrosine phosphorylation of c-Met on 
      human chondrosarcoma cell line HCS-2/8. The current study indicates that (a) CD44 
      stimulation by fragmented HA upregulates expression of c-Met proteins; (b) 
      fragmented HA also induces tyrosine phosphorylation of c-Met protein within 30 
      min, an early event in this pathway as shown by the early time course of 
      stimulation; (c) the effects of HA fragments are critically HA size-dependent. 
      High molecular weight HA is inactive, but lower molecular weight fragments (M(r) 
      3.5 kDa) are active with maximal effect in the microg/ml range; (d) the standard 
      form of CD44 (CD44s) is critical for the response because the effect on c-Met, 
      both in terms of upregulation and phosphorylation, is inhibited by preincubation 
      with an anti-CD44 monoclonal antibody; and (e) phosphorylation of c-Met induced 
      by CD44 stimulation is inhibited by protein tyrosine kinase inhibitor, 
      tyrphostin. Therefore, our study represents the first report that CD44 
      stimulation induced by fragmented HA enhances c-Met expression and tyrosine 
      phosphorylation in human chondrosarcoma cells. Taken together, these studies 
      establish a signal transduction cascade or cross-talk emanating from CD44 to 
      c-Met.
FAU - Suzuki, Mika
AU  - Suzuki M
AD  - Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, 
      Handayama 1-20-1, Handacho 3600, Hamamatsu, Shizuoka 431-3192, Japan.
FAU - Kobayashi, Hiroshi
AU  - Kobayashi H
FAU - Kanayama, Naohiro
AU  - Kanayama N
FAU - Nishida, Takashi
AU  - Nishida T
FAU - Takigawa, Masaharu
AU  - Takigawa M
FAU - Terao, Toshihiko
AU  - Terao T
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Hyaluronan Receptors)
RN  - 42HK56048U (Tyrosine)
RN  - 9004-61-9 (Hyaluronic Acid)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Chondrosarcoma/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Hyaluronan Receptors/*metabolism
MH  - Hyaluronic Acid/*metabolism/pharmacology
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-met/*metabolism
MH  - Tumor Cells, Cultured
MH  - Tyrosine/*metabolism
MH  - Up-Regulation/drug effects
EDAT- 2002/08/17 10:00
MHDA- 2002/09/24 06:00
CRDT- 2002/08/17 10:00
PHST- 2002/08/17 10:00 [pubmed]
PHST- 2002/09/24 06:00 [medline]
PHST- 2002/08/17 10:00 [entrez]
AID - S016748890200246X [pii]
AID - 10.1016/s0167-4889(02)00246-x [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2002 Aug 19;1591(1-3):37-44. doi: 
      10.1016/s0167-4889(02)00246-x.