Hoge
cholesterolwaarden bevorderen prostaatkanker.*
Uit
een studie met muizen blijkt dat hoge cholesterolwaarden prostaatkankercellen
doet groeien door chemische veranderingen teweeg te brengen in de kankercellen.
Hoge cholesterolwaarden deden geen nieuwe kankercellen ontstaan maar de
bestaande wel flink groeien. Als dan de cholesterolwaarden verlaagd werden werd
het proces omgekeerd en stopte de kankergroei.
High
Cholesterol Levels Accelerate Growth Of Prostate Cancer
Researchers
at Children's Hospital
Boston have demonstrated that high blood cholesterol levels
accelerate the growth of prostate tumors, showing
that cholesterol helps prostate tumors survive and
grow at the molecular level by altering chemical signaling patterns within tumor
cells.
The
findings, published an issue of the Journal of Clinical Investigation, are in
keeping with population studies that have linked prostate
cancer with high cholesterol levels and Western diets high in
cholesterol. The researchers also present evidence that cholesterol-lowering ''statin''
drugs, now widely used in cardiovascular disease, may inhibit cancer growth.
A
team led by Michael Freeman, PhD, Program Director of the Urological Diseases
Research Center at Children's, injected human prostate cancer cells into mice
and observed tumor growth. When the animals' blood cholesterol was raised by diet,
cholesterol accumulated in the outer membranes of the tumor cells, specifically
in structures called lipid rafts. Cholesterol elevation in the rafts activated a
chemical ''cell-survival'' pathway known as Akt, thought to be a central pathway
in prostate cancer. Activation of Akt enabled the tumor cells to resist chemical
cues to commit suicide through the process known as apoptosis, thereby allowing
the cancer to proliferate.
Increased
cholesterol levels didn't trigger new cancers in the mice, but six weeks after
tumor cells were injected, the incidence of tumors was more than doubled in the
mice on high-cholesterol diets, and the tumors were markedly larger in size. ''What
we're looking at is progression, not initiation of a tumor,'' says Freeman.
In
addition, test-tube studies showed that when the cholesterol-lowering drug
simvastatin was used to reduce cholesterol in cell membranes, the Akt pathway
was inhibited, apoptosis increased, and tumors stopped proliferating.
Replenishing cell membranes with cholesterol reversed this inhibitory effect.
''Our
study opens up a new paradigm in thinking about how cancer might be controlled
pharmacologically by manipulating cholesterol,'' says Freeman. ''Our data
support the notion that cholesterol-lowering drugs -- which are widely used and
fairly safe -- might be effective in prevention of prostate cancer, or as an
adjunctive therapy.''
Although
there is some epidemiologic evidence linking high cholesterol levels with
certain types of cancer, there has been little research at the cellular level to
try to explain why this is so. More recently, epidemiologic studies have begun
reporting that people taking cholesterol-lowering drugs have a significantly
reduced incidence of prostate and other cancers.
Lipid
rafts are structures in the outer cell membrane which Keith Solomon, PhD, a
co-investigator on the study and a lipid-raft expert, likens to ice floating on
water -- they are dynamic and continually aggregate and disaggregate. They have
naturally high concentrations of cholesterol and are believed to be important in
cell signaling. Solomon and Freeman believe that cholesterol in the lipid rafts
may help sequester proteins involved in cancer pathways in close proximity with
each other, facilitating biochemical reactions that promote cancer growth.
Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults for 136 years. More than 500 scientists, including eight members of the National Academy of Sciences, nine members of the Institute of Medicine and 10 members of the Howard Hughes Medical Institute comprise Children's research community. Founded in 1869 as a 20-bed hospital for children, Children's Hospital Boston today is a 325-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School. (November 2005)
