Elevated levels of epidermal growth factor (EGF) and epidermal growth
factor receptor (EGF-R) have been demonstrated in prostate cancer cell
lines and clinical specimens suggesting a role for polypeptide growth
factors in prostate tumor cell growth and invasion. To more clearly d
efine the role of EGF in prostate cancer invasion, we undertook a seri
es of studies utilizing the PC3 prostate cancer cell line, an aggressi
ve, hormone-independent cell line derived from a metastatic lesion. No
statistical differences were noted in the growth of PC3 cells under s
erum-free conditions when EGF (10(-10) M-10(-8) M) or monoclonal anti-
EGF-R antibody (10(-11) M-10(-8) M) were added. Utilizing the Boyden c
hamber microinvasion assay, EGF supplemented cells demonstrated a stat
istically significant augmentation in invasion (P < 0.05) when compare
d to control cells at each time point in the study. With increasing le
ngth of exposure to EGF, the number of concentrations that produced si
gnificant invasion increased: day 1 (10(-8) M), day 3 (10(-8), 10(-9)
M), and day 5 (10(-7), 10(-8), 10(-10) M). Northern blot analysis of E
GF supplemented cells revealed an increase in expression of urokinase
plasminogen activator (uPA) RNA, a serine protease involved in the reg
ulation of pericellular proteolysis and membrane degradation. Protein
analysis confirmed these findings. Statistically significant inhibitio
n of invasion by anti-uPA antibodies was demonstrated for EGF-stimulat
ed and PC3 control cells. Our results demonstrate that certain concent
rations of EGF augment invasion in the PC3 cell line. This enhancement
of invasion occurs in part by an overproduction of uPA, an extracellu
lar protease. These findings suggest that the autocrine production of
EGF may potentiate tumor cell invasion. (C) 1994 Wiley-Liss, Inc.