PMID- 17653103
OWN - NLM
STAT- MEDLINE
DCOM- 20080111
LR  - 20231120
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 15
IP  - 11
DP  - 2007 Nov
TI  - Human matrix metalloproteinase-8 gene delivery increases the oncolytic activity 
      of a replicating adenovirus.
PG  - 1982-90
AB  - The success of replicating adenoviruses for cancer therapy is limited by 
      inefficient virus delivery and poor distribution within the tumor mass. Stromal 
      matrix within the tumor may hinder the free cell-to-cell spread of the virus. In 
      this study, in vitro cell culture experiments showed that collagen I blocked the 
      passage of an adenoviral vector through a membrane. On the basis of reports of 
      the effective collagen I-degrading activity of matrix metalloproteinase-8 
      (MMP-8), we constructed an adenovirus to express the MMP-8 transgene (AdMMP8). 
      A549 cells infected in vitro with AdMMP8 did not show altered growth but were 
      able to modify a fibrillar collagen substrate to allow viral diffusion. Further, 
      AdMMP8 did not affect replication of the wild-type virus (Adwt300). Established 
      human A549 lung cancer and BxPC-3 pancreatic cancer xenograft tumors that were 
      injected with Adwt300 together with the non-replicating AdMMP8 virus showed 
      significantly reduced growth compared with control tumors. Histochemical analysis 
      showed reduced amounts of collagen within necrotic areas of MMP-8-injected tumors 
      compared with controls. These results demonstrate that intra-tumoral expression 
      of MMP-8 is a possible strategy for improving viral spread and improving the 
      oncolytic activity of replicating adenovirus.
FAU - Cheng, Jin
AU  - Cheng J
AD  - Division of Pulmonary and Critical Care Medicine, New York University School of 
      Medicine, New York, New York 10016, USA.
FAU - Sauthoff, Harald
AU  - Sauthoff H
FAU - Huang, YaoQi
AU  - Huang Y
FAU - Kutler, David I
AU  - Kutler DI
FAU - Bajwa, Sofia
AU  - Bajwa S
FAU - Rom, William N
AU  - Rom WN
FAU - Hay, John G
AU  - Hay JG
LA  - eng
GR  - M01RR-00096/RR/NCRR NIH HHS/United States
GR  - R01CA102053/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20070724
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (RNA, Messenger)
RN  - 9007-34-5 (Collagen)
RN  - EC 3.4.24.34 (Matrix Metalloproteinase 8)
SB  - IM
MH  - Adenoviridae/*physiology
MH  - Cell Line
MH  - Cell Survival
MH  - Collagen/metabolism
MH  - Gene Expression Regulation, Enzymologic
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Lung Neoplasms/*enzymology/genetics/*pathology
MH  - Matrix Metalloproteinase 8/genetics/*metabolism
MH  - RNA, Messenger/genetics
MH  - *Transduction, Genetic
MH  - *Virus Replication
EDAT- 2007/07/27 09:00
MHDA- 2008/01/12 09:00
CRDT- 2007/07/27 09:00
PHST- 2007/07/27 09:00 [pubmed]
PHST- 2008/01/12 09:00 [medline]
PHST- 2007/07/27 09:00 [entrez]
AID - S1525-0016(16)32661-2 [pii]
AID - 10.1038/sj.mt.6300264 [doi]
PST - ppublish
SO  - Mol Ther. 2007 Nov;15(11):1982-90. doi: 10.1038/sj.mt.6300264. Epub 2007 Jul 24.