Scientists find gas pedal -- and brake -- for uncontrolled cell growth

Aug 01, 2010

Researchers at the University of California, San Diego School of Medicine have identified a new way to regulate the uncontrolled growth of blood vessels, a major problem in a broad range of diseases and conditions.

The findings are published in the online edition of by David A. Cheresh, PhD, professor of pathology in the UC San Diego School of Medicine and associate director for translational research at the Moores UCSD Cancer Center, and colleagues at the cancer center and at the University of Michigan.

Blood vessels grow and expand in association with a number of diseases. In particular, new (known as angiogenesis) occurs during the growth of tumors, enabling them to expand and metastasize or spread to other parts of the body.

Uncontrolled vascular growth can lead to vascular malformations and hemangiomas, which may become life-threatening. According to the National Cancer Institute, as many as 500 million people worldwide could benefit from therapies targeting angiogenesis.

Researchers have been trying to identify the switch mechanism that converts normal blood vessels from the resting state to the proliferative or diseased state. Cheresh, along with the study's first author Sudarshan Anand, also of the UCSD School of Medicine and the Moores Cancer Center, and colleagues discovered how an "angiogenic switch" turns on and developed a strategy to turn it back off.

During normal blood vessel formation or regeneration, forming the inner layer of blood vessels are exposed to factors in the local microenvironment that initiate the switch, causing blood vessels to begin to expand. Cheresh and colleagues identified a small (miR-132) responsible for controlling the switch.

Cheresh described the process in terms of a car and its brakes:
"In tumor vessels or in hemangiomas, this particular microRNA is abundant and capable of maintaining extensive vascular growth. The effect is similar to a car that's speeding out of control because its gas pedal is stuck to the floor and its brakes aren't working."

The researchers designed a complementary microRNA, or anti-miR, that binds to and neutralizes the original microRNA. "This anti-miR therapy in effect restores functionality to the brake pedal and uncontrolled blood vessel growth comes to a halt," said Cheresh, who noted the new anti-miR turned off the angiogenic switch controlling disease severity in mouse models of cancer and of retinal disorders.

As part of their study, Cheresh and colleagues designed a nanoparticle that's capable of delivering the microRNA or the anti-microRNA directly to the diseased or proliferating . This delivery vehicle ensures the therapeutic benefit is maximized while reducing the possibility of toxicity or side effects.

By delivering more of this microRNA, the scientists said, it may be possible to promote new blood vessel development in patients who have suffered tissue damage from stroke, heart attacks, or diabetes. Conversely, treating patients with the anti-miR might reduce or inhibit blood vessel development in tumors or help reduce inflammation.

Explore further: Novel marker discovered for stem cells derived from human umbilical cord blood

Related Stories

Researchers create drug to keep tumor growth switched off

Feb 11, 2010

A novel -- and rapid -- anti-cancer drug development strategy has resulted in a new drug that stops kidney and pancreatic tumors from growing in mice. Researchers at the Moores Cancer Center at the University of California, ...

Precancerous stem cells can form tumor blood vessels

Feb 20, 2008

Tumors require a blood supply to grow, but how they acquire their network of blood vessels is poorly understood. A new study here shows that tumor blood vessels can develop from precancerous stem cells, a recently discovered ...

Recommended for you

New pain relief targets discovered

9 hours ago

Scientists have identified new pain relief targets that could be used to provide relief from chemotherapy-induced pain. BBSRC-funded researchers at King's College London made the discovery when researching ...

Building 'smart' cell-based therapies

9 hours ago

A Northwestern University synthetic biology team has created a new technology for modifying human cells to create programmable therapeutics that could travel the body and selectively target cancer and other ...

Proper stem cell function requires hydrogen sulfide

12 hours ago

Stem cells in bone marrow need to produce hydrogen sulfide in order to properly multiply and form bone tissue, according to a new study from the Center for Craniofacial Molecular Biology at the Herman Ostrow School of Dentistry ...

User comments : 0

More news stories

Chronic inflammation linked to 'high-grade' prostate cancer

Men who show signs of chronic inflammation in non-cancerous prostate tissue may have nearly twice the risk of actually having prostate cancer than those with no inflammation, according to results of a new study led by researchers ...

Turning off depression in the brain

Scientists have traced vulnerability to depression-like behaviors in mice to out-of-balance electrical activity inside neurons of the brain's reward circuit and experimentally reversed it – but there's ...

Better thermal-imaging lens from waste sulfur

Sulfur left over from refining fossil fuels can be transformed into cheap, lightweight, plastic lenses for infrared devices, including night-vision goggles, a University of Arizona-led international team ...

Hackathon team's GoogolPlex gives Siri extra powers

(Phys.org) —Four freshmen at the University of Pennsylvania have taken Apple's personal assistant Siri to behave as a graduate-level executive assistant which, when asked, is capable of adjusting the temperature ...