PMID- 20798956
OWN - NLM
STAT- MEDLINE
DCOM- 20110119
LR  - 20191210
IS  - 1432-0878 (Electronic)
IS  - 0302-766X (Linking)
VI  - 342
IP  - 1
DP  - 2010 Oct
TI  - TIMP-1 interaction with alphavbeta3 integrin confers resistance to human osteosarcoma 
      cell line MG-63 against TNF-alpha-induced apoptosis.
PG  - 87-96
LID - 10.1007/s00441-010-1025-1 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine affecting diverse 
      cellular responses. TNF-alpha is cytotoxic in many systems, but it can also act as an 
      anti-apoptotic signal to promote cell survival pathways activated through 
      integrins and extracellular matrix components. This is particularly evident in 
      cancer cells. To unravel the basis of resistance to TNF-alpha-induced apoptosis, 
      human osteosarcoma MG-63 cell line was used. Our data showed that resistance to 
      apoptosis was accompanied by high levels of TIMP-1 expression in part mediated by 
      NF-kappaB activation, whereas under apoptotic conditions, in the presence of 
      cycloheximide (CHX), TIMP-1 and alphavbeta3 integrin protein levels were significantly 
      reduced. Silencing TIMP-1 using siRNA led to increased apoptosis following 
      treatment with TNF-alpha, whereas exogenously-added recombinant TIMP-1 reduced the 
      extent of apoptosis. Immunoprecipitation and confocal microscopy experiments 
      demonstrated that TIMP-1 interacted with alphavbeta3 integrins. The biological role of 
      this interaction was revealed by the use of echistatin, an antagonist of alphavbeta3 
      integrin. In the presence of echistatin, decreased protection against apoptosis 
      by recombinant TIMP-1 was observed.
FAU - Tsagaraki, Ioanna
AU  - Tsagaraki I
AD  - Institute of Biology, National Center for Scientific Research Demokritos, 15310 
      Agia Paraskevi, Athens, Greece.
FAU - Tsilibary, Effie C
AU  - Tsilibary EC
FAU - Tzinia, Athina K
AU  - Tzinia AK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100828
PL  - Germany
TA  - Cell Tissue Res
JT  - Cell and tissue research
JID - 0417625
RN  - 0 (Integrin alphaVbeta3)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Peptides)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 118337-11-4 (echistatin)
RN  - 98600C0908 (Cycloheximide)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Cell Line, Tumor
MH  - Cycloheximide/pharmacology
MH  - Drug Resistance, Neoplasm/*drug effects
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Humans
MH  - Integrin alphaVbeta3/*metabolism
MH  - Intercellular Signaling Peptides and Proteins
MH  - NF-kappa B/metabolism
MH  - Osteosarcoma/*metabolism/pathology
MH  - Peptides/pharmacology
MH  - Platelet Aggregation Inhibitors/pharmacology
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - Tissue Inhibitor of Metalloproteinase-1/*biosynthesis
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2010/08/28 06:00
MHDA- 2011/01/20 06:00
CRDT- 2010/08/28 06:00
PHST- 2010/04/29 00:00 [received]
PHST- 2010/07/21 00:00 [accepted]
PHST- 2010/08/28 06:00 [entrez]
PHST- 2010/08/28 06:00 [pubmed]
PHST- 2011/01/20 06:00 [medline]
AID - 10.1007/s00441-010-1025-1 [doi]
PST - ppublish
SO  - Cell Tissue Res. 2010 Oct;342(1):87-96. doi: 10.1007/s00441-010-1025-1. Epub 2010 
      Aug 28.