Study identifies another strategy for normalizing tumor blood supply

February 20, 2008

Manipulating levels of nitric oxide (NO), a gas involved in many biological processes, may improve the disorganized network of blood vessels supplying tumors, potentially improving the effectiveness of radiation and chemotherapy.

In an upcoming issue of the journal Nature Medicine, researchers from the Steele Laboratory of Radiation Oncology at Massachusetts General Hospital (MGH) report an experiment in which NO production was selectively suppressed in tumor cells while being maintained in blood vessels. The result was a significant improvement in the appearance and function of the tumor’s blood supply.

“Our finding suggest that the creation of perivascular NO gradients – differences between the levels produced in blood vessels and those found in tumor tissue – may be able to normalize tumor vasculature,” says Dai Fukumura, MD, PhD, of the Steele Laboratory, who led the study. “Combining the use of angiogenesis inhibitors, which normalize vasculature through a different mechanism, with the blockade of nonvascular NO production may produce even greater improvement in therapeutic outcomes.”

The blood vessels that develop around and within tumors are leaky and disorganized, interfering with delivery of chemotherapy drugs and with radiation treatment, which requires an adequate oxygen supply. Combining angiogenesis inhibitors, drugs that suppress the growth of blood vessels, with traditional anticancer therapies has improved patient survival in some tumors. That success supports a theory developed by Rakesh K. Jain, PhD, director of the Steele Laboratory, that the agents temporarily ‘normalize’ blood vessels, creating a period during which other treatments can be more effective.

Since angiogenesis is one of many physiologic activities mediated by NO, the MGH research team hypothesized that restricting NO production to blood vessels also could improve tumor vasculature. Using cancer cells from human brain tumors, they suppressed the enzyme that controls NO production in nonvascular tissue. When the modified tumor cells were implanted into mice, analysis of the resulting tumors showed that NO was present primarily in blood vessels, with significant reductions in tumor cells. Vessels in the growing tumors were more evenly distributed and less distorted than those in tumors grown from untreated tissue.

“Angiogenesis inhibitors block formation of new vessels by directly or indirectly inhibiting the proliferation and survival of vascular endothelial cells. But since their overall effect is to reduce the density of blood vessels, the ability of those agents to normalize tumor vasculature may not last long,” says Fukumura. “Blocking nonvascular NO production and maintaining NO levels around the vessels appears to keep endothelial cell function at the proper level.” An associate professor of Radiation Oncology at Harvard Medical School, Fukumura notes that the strategy now should be investigated in other types of tumors.

Source: Massachusetts General Hospital

Explore further: Scientists reveal link between cell metabolism and the spread of cancer

Related Stories

New treatment approved for soft-tissue cancers

October 19, 2016

(HealthDay)—Lartruvo (olaratumab) has been approved by the U.S. Food and Drug Administration to treat adults with certain soft-tissue sarcomas, cancers that develop in areas such as the muscles, fat, blood vessels and tendons.

Study applies math to describe tumor growth

October 17, 2016

Universidad Carlos III de Madrid (UC3M) has carried out a study that mathematically explains how tumors induce the growth of blood vessels. The study maintains that the tips of the blood vessels expand like a soliton, a solitary ...

Easing excruciating facial nerve pain

October 6, 2016

For more than a year, Surujdai Kalladeen suffered excruciating pain in her face that would render her unable to work or do anything for long stretches of time. After seeking help from several doctors, including a neurologist ...

Recommended for you

Natural compound reduces signs of aging in healthy mice

October 27, 2016

Much of human health hinges on how well the body manufactures and uses energy. For reasons that remain unclear, cells' ability to produce energy declines with age, prompting scientists to suspect that the steady loss of efficiency ...

A metabolic switch to turn off obesity

October 27, 2016

You've tried all the diets. No matter: you've still regained the weight you lost, even though you ate well and you exercised regularly! This may be due to a particular enzyme in the brain: the alpha/beta hydrolase domain-6 ...

Mitochondria control stem cell fate

October 27, 2016

What happens in intestinal epithelial cells during a chronic illness? Basic research conducted at the Chair of Nutrition and Immunology at the Technical University of Munich (TUM) addressed this question by generating a new ...

Scientists develop 'world-first' 3-D mammary gland model

October 27, 2016

A team of researchers from Cardiff University and Monash Biomedicine Discovery Institute has succeeded in creating a three-dimensional mammary gland model that will pave the way for a better understanding of the mechanisms ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.