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New Research Model of Human Prostate Cancer
shows Cancer Development
Newswise — Progress toward understanding the
role of sex hormones in the growth of
prostate cancer—the most common cancer in
U.S. men—has been hindered by the lack of a
suitable laboratory research model. Now
researchers say they have developed the
first model of hormone-induced human
prostate cancer initiation and progression.
Their results were presented at The Endocrine
Society’s 92nd Annual Meeting in San Diego.
“We hope this model will speed up the process
of testing preventive therapies for prostate
cancer as well as help clarify the hormonal
mechanisms in the development of this
cancer,” said Gail Prins, PhD, a professor
and reproductive physiologist at the
University of Illinois at Chicago, who is a
co-author of the study.
“Sex hormones—testosterone and estrogens—are
involved in regulating the growth of
prostate cancer, but the mechanisms are not
well established,” Prins said.
Currently the only available laboratory
models of human prostate cancer are
xenografts—cancerous human tissues grafted
under the skin of animals—or “transformed”
cancer cell lines containing cells that
originally came from patients with prostate
cancer. However, Prins said, “If you want to
study the initial development of
cancer—either naturally or induced—or its
prevention, you cannot use a model of
existing cancer, such as transformed cell
lines.”
To study the progression of prostate cancer
from normal cells into cancerous cells
requires the use of animal prostate cells.
Animal models, however, do not directly
mimic all aspects of human prostate cancer,
experts say.
Prins and her colleagues created their model
using prostate cells obtained from a
deceased organ donor who did not have
prostate disease. They isolated and grew, in
3-D culture, adult prostate progenitor
cells—cells with stem cell-like properties
that self-renew and may become cancerous. In
3-D culture, the progenitor cells
proliferate and form small spheroids, called
prostaspheres, which are capable of
regenerating tissues.
The researchers combined these human
prostaspheres with embryonic cells from the
prostate of a rat and then transplanted the
mixed cells under the kidney capsule of
mice. These transplants regenerated into
normal human prostate-like tissues and
secreted prostate-specific antigen (PSA),
which confirmed human functionality,
according to Prins.
The mice then received a drug pellet
containing testosterone and estradiol
estrogen. A cancerous tumor formed at the
transplant site.
“We were able to induce hormonally driven
prostate cancer in these recombinant
tissues,” Prins said. “Using this model, we
can follow the entire pathway of the
cancer—from normal tissue to initiation and
progression.”