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: Does lactate, the bane of athletes, help drive cancer?

Related Stories

Does lactate, the bane of athletes, help drive cancer?

March 15, 2017

For decades, lactate has been studied largely in the context of exercise, painted as a nagging metabolic byproduct that accumulates in the tissues and blood during workouts, stiffening muscles and hindering performance.

Scientists create three-dimensional bladder reconstruction

March 16, 2017

The way doctors examine the bladder for tumors or stones is like exploring the contours of a cave with a flashlight. Using cameras attached to long, flexible instruments called endoscopes, they find that it's sometimes difficult ...

Reprogrammed blood vessels promote cancer spread

March 3, 2017

Blood vessels play a critical role in the growth and spread of cancer. The cells lining the inner wall of blood vessels (endothelial cells) and cancer cells are in close contact to each other and mutually influence each other. ...

MRI-powered mini-robots could offer targeted treatment

March 7, 2017

Invasive surgical techniques - cutting through the breastbone for open heart surgery or making a large incision to inspect an abdominal tumor - allow physicians to effectively treat disease but can lead to sometimes serious ...

Recommended for you

How the nervous system controls tumor growth

March 22, 2017

(Medical Xpress)—From the time it first comes online during development the nervous system begins to exact precise control over many biologic functions. In some cases, too much control. When it does, a little nerve-squelching ...

Surprising new role for lungs—making blood

March 22, 2017

Using video microscopy in the living mouse lung, UC San Francisco scientists have revealed that the lungs play a previously unrecognized role in blood production. As reported online March 22, 2017 in Nature, the researchers ...

Using a smartphone to screen for male infertility

March 22, 2017

More than 45 million couples worldwide grapple with infertility, but current standard methods for diagnosing male infertility can be expensive, labor-intensive and require testing in a clinical setting. Cultural and social ...

Weight-bearing exercises promote bone formation in men

March 22, 2017

Osteoporosis affects more than 200 million people worldwide and is a serious public health concern, according to the National Osteoporosis Foundation. Now, Pamela Hinton, associate professor in the Department of Nutrition ...

0 comments

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.