PMID- 9722624
OWN - NLM
STAT- MEDLINE
DCOM- 19980925
LR  - 20190508
IS  - 0021-9525 (Print)
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Linking)
VI  - 142
IP  - 4
DP  - 1998 Aug 24
TI  - Growth factor-dependent activation of alphavbeta3 integrin in normal epithelial 
      cells: implications for tumor invasion.
PG  - 1145-56
AB  - Integrin activation is a multifaceted phenomenon leading to increased affinity 
      and avidity for matrix ligands. To investigate whether cytokines produced during 
      stromal infiltration of carcinoma cells activate nonfunctional epithelial 
      integrins, a cellular system of human thyroid clones derived from normal glands 
      (HTU-5) and papillary carcinomas (HTU-34) was employed. In HTU-5 cells, 
      alphavbeta3 integrin was diffused all over the membrane, disconnected from the 
      cytoskeleton, and unable to mediate adhesion. Conversely, in HTU-34 cells, 
      alphavbeta3 was clustered at focal contacts (FCs) and mediated firm attachment 
      and spreading. alphavbeta3 recruitment at FCs and ligand-binding activity, 
      essentially identical to those of HTU-34, occurred in HTU-5 cells upon treatment 
      with hepatocyte growth factor/scatter factor (HGF/SF). The HTU-34 clone secreted 
      HGF/SF and its receptor was constitutively tyrosine phosphorylated suggesting an 
      autocrine loop responsible for alphavbeta3 activated state. Antibody-mediated 
      inhibition of HGF/SF function in HTU-34 cells disrupted alphavbeta3 enrichment at 
      FCs and impaired adhesion. Accordingly, activation of alphavbeta3 in normal cells 
      was produced by HTU-34 conditioned medium on the basis of its content of HGF/SF. 
      These results provide the first example of a growth factor-driven integrin 
      activation mechanism in normal epithelial cells and uncover the importance of 
      cytokine-based autocrine loops for the physiological control of integrin 
      activation.
FAU - Trusolino, L
AU  - Trusolino L
AD  - DIBIT, Department of Biological and Technological Research, San Raffaele 
      Scientific Institute, 20132 Milano, Italy.
FAU - Serini, G
AU  - Serini G
FAU - Cecchini, G
AU  - Cecchini G
FAU - Besati, C
AU  - Besati C
FAU - Ambesi-Impiombato, F S
AU  - Ambesi-Impiombato FS
FAU - Marchisio, P C
AU  - Marchisio PC
FAU - De Filippi, R
AU  - De Filippi R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Antigens, CD)
RN  - 0 (Cytokines)
RN  - 0 (Integrin beta1)
RN  - 0 (Integrin beta3)
RN  - 0 (Platelet Membrane Glycoproteins)
RN  - 42HK56048U (Tyrosine)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Antigens, CD/*metabolism
MH  - Cell Adhesion/*physiology
MH  - Cell Movement/physiology
MH  - Clone Cells/metabolism
MH  - Cytokines/*physiology
MH  - Cytoskeleton/physiology
MH  - Extracellular Matrix/metabolism
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique
MH  - Hepatocyte Growth Factor/*pharmacology
MH  - Humans
MH  - Integrin beta1/metabolism
MH  - Integrin beta3
MH  - Neoplasm Invasiveness/*physiopathology
MH  - Neoplasm Metastasis
MH  - Phosphorylation
MH  - Platelet Membrane Glycoproteins/*metabolism
MH  - Proto-Oncogene Proteins c-met/metabolism
MH  - Signal Transduction
MH  - Thyroid Gland/physiology
MH  - Tumor Cells, Cultured
MH  - Tyrosine/metabolism
PMC - PMC2132885
EDAT- 1998/08/29 00:00
MHDA- 1998/08/29 00:01
PMCR- 1999/02/24
CRDT- 1998/08/29 00:00
PHST- 1998/08/29 00:00 [pubmed]
PHST- 1998/08/29 00:01 [medline]
PHST- 1998/08/29 00:00 [entrez]
PHST- 1999/02/24 00:00 [pmc-release]
AID - 10.1083/jcb.142.4.1145 [doi]
PST - ppublish
SO  - J Cell Biol. 1998 Aug 24;142(4):1145-56. doi: 10.1083/jcb.142.4.1145.