Prostate cancer cells, as well as some other solid tumors, have
been shown to contain higher cholesterol levels than normal cells.
Now a team led by researchers at the Duke Cancer Institute have
identified a cellular process that cancer cells hijack to hoard
cholesterol and fuel their growth. Identifying this process could inform
the development of better ways to control cholesterol accumulation in
tumors, potentially leading to improved survival for prostate cancer
patients.
‘A cellular process that cancer cells hijack to hoard cholesterol and fuel their growth has been identified by researchers.’
The findings are published online this month in the journal
Cancer Research.
Donald McDonnell, chairman of the Department of
Pharmacology and Cancer Biology at Duke, said, "All cells need cholesterol to
grow, and too much of it can stimulate uncontrolled growth. Prostate cancer cells somehow bypass the cellular control switch
that regulates the levels of cholesterol allowing them to accumulate
this fat. This process has not been well understood.
In this study, we show how prostate cancer cells accomplish this."
McDonnell and colleagues began by identifying genes involved in
cholesterol regulation in prostate tumors. They homed in on a specific
gene, CYP27A1, which is a key component of the machinery that governs
the level of cholesterol within cells.
In patients with prostate cancer, the expression of the CYP27A1 gene
in tumors is significantly lower, and this is especially true for men
with aggressive cancers compared to the tumors in men with more benign
disease. Downregulation of this gene basically shuts off the sensor that
cells use to gauge when they have taken up enough cholesterol. This in
turn allows accumulation of this fat in tumor cells. Access to more
cholesterol gives prostate cancer cells a selective growth advantage.
"It remains to be determined how this regulatory activity can be
restored and/or
whether it's possible to mitigate the effects of the increased
cholesterol uptake that result from the loss of CYP27A1 expression,"
McDonnell said.
He said statin use alone might help, but perhaps not enough, since
tumors could simply rev up the regulation of the cholesterol
manufacturing process in tumors to compensate.
McDonnell said is lab is continuing the research, including finding
ways to induce cells to eject cholesterol, reverse the inhibition of
CYP27A1 activity, or introduce compounds that interfere with
cholesterol-production in the tumor.
Source: Eurekalert
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