Nav: Home

Prostate cancer cells grow with malfunction of cholesterol control in cells

February 21, 2017

DURHAM, N.C. - Advanced prostate cancer and high blood cholesterol have long been known to be connected, but it has been a chicken-or-egg problem.

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.

The findings are published online this month in the journal Cancer Research.

"Prostate cancer cells, as well as some other solid tumors, have been shown to contain higher cholesterol levels than normal cells," said senior author Donald McDonnell, Ph.D., chairman of the Department of Pharmacology and Cancer Biology at Duke. "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," McDonnell said. "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.
-end-
In addition to McDonnell, study authors include Mahmoud A. Alfaqih, Erik R. Nelson, Wen Liu, Rachid Safi, Jeffery S. Jasper, Everardo Macias, Joseph Geradts, J. Will Thompson, Laura G. Dubois, Michael R. Freeman, Ching-yi Chang, Jen-Tsan Chi, and Stephen J. Freedland.

This work received funding from the National Institutes of Health (R01DK048807, R00CA172357, 3R01-CA125618-08S1, CA131235 and 5K24CA160653-03); The Stewart Rahr Prostate Cancer Foundation Young Investigator Award and the Department of Defense (W81XWH-12-1-0102).

Duke University Medical Center

Related Prostate Cancer Articles:

ASCO and Cancer Care Ontario update guideline on radiation therapy for prostate cancer
The American Society of Clinical Oncology (ASCO) and Cancer Care Ontario today issued a joint clinical practice guideline update on brachytherapy (internal radiation) for patients with prostate cancer.
Patient prostate tissue used to create unique model of prostate cancer biology
For the first time, researchers have been able to grow, in a lab, both normal and primary cancerous prostate cells from a patient, and then implant a million of the cancer cells into a mouse to track how the tumor progresses.
Moffitt Cancer Center awarded $3.2 million grant to study bone metastasis in prostate cancer
Moffitt researchers David Basanta, Ph.D., and Conor Lynch, Ph.D., have been awarded a U01 grant to investigate prostate cancer metastasis.
New findings concerning hereditary prostate cancer
For the first time ever, researchers have differentiated the risks of developing indolent or aggressive prostate cancer in men with a family history of the disease.
Prostate cancer discovery may make it easier to kill cancer cells
A newly discovered connection between two common prostate cancer treatments may soon make prostate cancer cells easier to destroy.
New test for prostate cancer significantly improves prostate cancer screening
A study from Karolinska Institutet in Sweden shows that a new test for prostate cancer is better at detecting aggressive cancer than PSA.
The dilemma of screening for prostate cancer
Primary care providers are put in a difficult position when screening their male patients for prostate cancer -- some guidelines suggest that testing the general population lacks evidence whereas others state that it is appropriate in certain patients.
Risk factors for prostate cancer
New research suggests that age, race and family history are the biggest risk factors for a man to develop prostate cancer, although high blood pressure, high cholesterol, vitamin D deficiency, inflammation of prostate, and vasectomy also add to the risk.
Prostate cancer is 5 different diseases
Cancer Research UK scientists have for the first time identified that there are five distinct types of prostate cancer and found a way to distinguish between them, according to a landmark study published today in EBioMedicine.
UH Seidman Cancer Center performs first-ever prostate cancer treatment
The radiation oncology team at UH Seidman Cancer Center in Cleveland performed the first-ever prostate cancer treatment April 3 using a newly-approved device -- SpaceOAR which enhances the efficacy of radiation treatment by protecting organs surrounding the prostate.

Related Prostate Cancer Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#529 Do You Really Want to Find Out Who's Your Daddy?
At least some of you by now have probably spit into a tube and mailed it off to find out who your closest relatives are, where you might be from, and what terrible diseases might await you. But what exactly did you find out? And what did you give away? In this live panel at Awesome Con we bring in science writer Tina Saey to talk about all her DNA testing, and bioethicist Debra Mathews, to determine whether Tina should have done it at all. Related links: What FamilyTreeDNA sharing genetic data with police means for you Crime solvers embraced...