PMID- 17452979
OWN - NLM
STAT- MEDLINE
DCOM- 20071107
LR  - 20220409
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 26
IP  - 44
DP  - 2007 Sep 27
TI  - An osteopontin fragment is essential for tumor cell invasion in hepatocellular 
      carcinoma.
PG  - 6361-71
AB  - Tumor cell invasion is a primary event in the metastatic progression of 
      hepatocellular carcinoma (HCC). Our recent results indicate a concordant elevated 
      expression of osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9) in primary 
      metastatic HCC. This study hypothesizes an MMP-9-directed cleavage of OPN that 
      biologically contributes to HCC metastasis. We found that MMP-9 cleaved OPN into 
      specific fragments in vitro, of which three could be identified by Edman 
      degradation amino-acid sequencing. One of these fragments (OPN-5 kDa, residues 
      167-210) induced low-metastatic HCC cellular invasion via CD44 receptors, which 
      was effectively blocked by the addition of small peptides within the region of 
      OPN-5 kDa. Increased expression of an OPN splice variant (OPN-c) was associated 
      with clinical metastatic HCC. Overexpression of OPN-c with physiological levels 
      of MMP-9 enhanced cellular invasion and coincided with elevated OPN-5 kDa levels. 
      Our data suggest that an alternative splicing event (OPN-c) promotes 
      extracellular cleavage of OPN by MMP-9, thus releasing a distinct region of OPN 
      (OPN-5 kDa) that is essential for HCC cellular invasion and appears to correlate 
      with metastatic potential. The findings of this study may help to improve 
      advanced-stage HCC prognosis and suggest the utility of small peptides for novel 
      therapies.
FAU - Takafuji, V
AU  - Takafuji V
AD  - Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer 
      Institute, National Institutes of Health, Bethesda, MD 20892-4258, USA.
FAU - Forgues, M
AU  - Forgues M
FAU - Unsworth, E
AU  - Unsworth E
FAU - Goldsmith, P
AU  - Goldsmith P
FAU - Wang, X W
AU  - Wang XW
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20070423
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (Peptide Fragments)
RN  - 0 (RNA, Messenger)
RN  - 106441-73-0 (Osteopontin)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Alternative Splicing
MH  - Animals
MH  - Blotting, Western
MH  - Carcinoma, Hepatocellular/metabolism/*secondary
MH  - Cell Adhesion
MH  - Cell Movement
MH  - Chromatography, Affinity
MH  - Disease Progression
MH  - Gene Expression Regulation, Neoplastic/physiology
MH  - Humans
MH  - Hyaluronan Receptors/metabolism
MH  - Immunoprecipitation
MH  - Liver Neoplasms/genetics/metabolism/*pathology
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Neoplasm Invasiveness
MH  - Osteopontin/*physiology
MH  - Peptide Fragments/*physiology
MH  - Prognosis
MH  - RNA, Messenger/genetics/metabolism
MH  - Rabbits
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transfection
EDAT- 2007/04/25 09:00
MHDA- 2007/11/08 09:00
CRDT- 2007/04/25 09:00
PHST- 2007/04/25 09:00 [pubmed]
PHST- 2007/11/08 09:00 [medline]
PHST- 2007/04/25 09:00 [entrez]
AID - 1210463 [pii]
AID - 10.1038/sj.onc.1210463 [doi]
PST - ppublish
SO  - Oncogene. 2007 Sep 27;26(44):6361-71. doi: 10.1038/sj.onc.1210463. Epub 2007 Apr 
      23.