Llwk. Chung et al., DEVELOPMENT OF HUMAN PROSTATE-CANCER MODELS FOR CHEMOPREVENTION AND EXPERIMENTAL THERAPEUTICS STUDIES, Journal of cellular biochemistry, 1997, pp. 174-181
The progression of human prostate cancer from histomorphologic to clin
ical expression often requires several decades. This study emphasizes
the importance of developing relevant human prostate cancer models to
study the molecular events leading to prostate cancer progression. The
se models will provide a rational basis for chemopreventive and treatm
ent strategies to retard the progression of human prostate cancer from
its localized to its metastatic state. In our laboratory, we have est
ablished the LNCaP progression and ARCaP models and the in vitro three
-dimensional growth models involving prostate cancer and bone stroma t
o study the progression of prostate cancer. We propose that prostate c
ancer may progress from an androgen-dependent to an androgen-independe
nt stale. While existing as androgen-independent tumors (defined as tu
mors capable of growing in castrated hosts and secreting PSA in serum)
, prostate cancer may assume three different phenotypes as it progress
es: androgen-independent while remaining androgen-responsive; androgen
-independent and unresponsive to androgen stimulation; and androgen-in
dependent but suppressed by androgen. It is conceivable that any andro
gen-independent human prostate cancer may contain variable proportions
of cells that exhibit these three phenotypes. This concept may have i
mportant implications in determining strategies for chemopreventive an
d therapeutic trials. We have established three-dimensional growth mod
els of prostate cancer cells either in collagen gel or microgravity-si
mulated growth conditions to form viable and functional organoids whic
h contain prostate cancer epithelial cells admired with prostate or bo
ne stromal cells. These in vitro models combined with the in vivo mode
ls described above will enhance our understanding of the regulatory me
chanism of prostate cancer growth and progression, and hence could imp
rove efficiency in screening chemopreventive and therapeutic agents wh
ich alter the biologic behaviors of human prostate cancer. (C) 1998 Wi
ley-Liss, Inc.