PMID- 10417342
OWN - NLM
STAT- MEDLINE
DCOM- 19990916
LR  - 20181113
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 341 ( Pt 3)
IP  - Pt 3
DP  - 1999 Aug 1
TI  - Autocrine regulation of growth stimulation in human epithelial ovarian carcinoma 
      by serine-proteinase-catalysed release of the urinary-type-plasminogen-activator 
      N-terminal fragment.
PG  - 765-9
AB  - Ovarian carcinomas secrete single-chain urinary-type plasminogen activator 
      (scuPA) and expression of uPA is up-regulated relative to normal ovarian 
      epithelium, leading to an enhanced proteolytic capacity which may facilitate 
      invasion. Furthermore, the uPA receptor (uPAR) is present on ovarian carcinoma 
      cells and is occupied in tumour tissues. In the present study, incubation of 
      scuPA with serum-free conditioned medium from ovarian carcinoma cells resulted in 
      release of a 14 kDa polypeptide. N-terminal sequence analysis identified this 
      fragment as the uPA N-terminal fragment (NTF), which contains a growth-factor and 
      a kringle domain. NTF generation was abolished by serine-proteinase inhibitors, 
      but not inhibitors of matrix metalloproteinases, and was not enhanced by the 
      addition of plasminogen or plasmin. To determine whether ovarian carcinoma-cell 
      growth is altered by uPA, the effect of exogenous scuPA or NTF on proliferation 
      was analysed. Both NTF and scuPA induced a dose-dependent increase in 
      proliferation, with maximal stimulation obtained at 10-20 nM. Furthermore, 
      blocking the interaction of endogenous uPA with uPAR using anti-NTF antibodies 
      significantly inhibited proliferation. Together these data indicate that, in 
      addition to enhancing the invasive activity of ovarian carcinoma cells via 
      increased pericellular proteolysis, uPA also acts as a mitogen for ovarian 
      carcinoma cells, suggesting a biochemical mechanism whereby uPA may contribute to 
      ovarian carcinoma progression by modulating both cell invasion and proliferation.
FAU - Fishman, D A
AU  - Fishman DA
AD  - Department of Obstetrics and Gynecology, Northwestern University Medical School, 
      Chicago, IL 60611, USA.
FAU - Kearns, A
AU  - Kearns A
FAU - Larsh, S
AU  - Larsh S
FAU - Enghild, J J
AU  - Enghild JJ
FAU - Stack, M S
AU  - Stack MS
LA  - eng
GR  - CA 58900/CA/NCI NIH HHS/United States
GR  - HL 49542/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Peptide Fragments)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
SB  - IM
MH  - Cell Division/*drug effects
MH  - Female
MH  - Humans
MH  - Ovarian Neoplasms/metabolism/*pathology
MH  - Peptide Fragments/*metabolism
MH  - Serine Endopeptidases/*metabolism
MH  - Urokinase-Type Plasminogen Activator/*chemistry
PMC - PMC1220416
EDAT- 1999/07/27 00:00
MHDA- 1999/07/27 00:01
PMCR- 2000/02/01
CRDT- 1999/07/27 00:00
PHST- 1999/07/27 00:00 [pubmed]
PHST- 1999/07/27 00:01 [medline]
PHST- 1999/07/27 00:00 [entrez]
PHST- 2000/02/01 00:00 [pmc-release]
PST - ppublish
SO  - Biochem J. 1999 Aug 1;341 ( Pt 3)(Pt 3):765-9.