In vitro regulation of pericellular proteolysis in prostatic tumor cells treated with bombesin

Claudio Festuccia, Fulvio Guerra, Sandra D'Ascenzo, Daniela Giunciuglio, Adriana Albini, Mauro Bologna

Research output: Contribution to journalArticle

Abstract

Bombesin is a potent inducer of signal trasduction pathways involved in the proliferation and invasion of androgen-insensitive prostatic tumor cells. This study examines the bombesin-mediated modulation of pericellular proteolysis, monitoring cell capability to migrate and invade basement membranes, using a chemo-invasion assay and analyzing protease production. The results suggest that bombesin could modulate the invasive potential of prostatic cell lines regulating secretion and cell-surface uptake of uPA and MMP-9 activation. In fact, in PC3 and DUI45 cells but not in LNCaP cells, urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-I (PAI-I) are induced by bombesin treatment. Bombesin also stimulates cell proliferation and this effect can be inhibited blocking uPA by antibodies and/or uPA inhibitor p-aminobenzamidine. Moreover, HMW-uPA induces cell proliferation in LNCaP cells, which do not produce uPA in the basal conditions, while PC3 and DUI45 cell growth is supported by autotrine production of uPA. The increment of uPA activity on the external plasma membrane causes an increased pericellular plasmin activation. This effect is inhibited by antibodies against uPA and by p-aminobenzamidine. Similarly to EGF, bombesin stimulates secretion and activation of MMP-9 and TIMP-I production. MMP-9 activation can be also obtained by HPIW-uPA treatment, suggesting that plasma-membrane-bound uPA can start a proteolytic cascade involving MMP-9. Therefore, in in vitro assays, bombesin is able to modulate pericellular proteolysis and cell proliferation, differently distributing and activating proteolytic activities. This effect can be related to the 'non- random' degradation of the extracellular matrix in which membrane uPA- uPAreceptor complexes could start bombesin-induced directional protein degradation during metastatic spread.

Original languageEnglish
JournalInternational Journal of Cancer
Volume75
Issue number3
DOIs
Publication statusPublished - Jan 30 1998

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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