Featured Research

from universities, journals, and other organizations

'Normalizing' Tumor Vessels Leaves Cancer More Benign

Date:
February 21, 2009
Source:
Cell Press
Summary:
New research suggests a counterintuitive new method to make cancer less likely to spread: by normalizing the shape of tumors' blood vessels to improve their oxygen supply. Such a treatment strategy might also boost the efficacy and reduce resistance to available anti-cancer drugs and so-called anti-angiogenic drugs that work by cutting off the growth of new blood vessels.

A new report suggests a counterintuitive new method to make cancer less likely to spread: by normalizing the shape of tumors' blood vessels to improve their oxygen supply. Such a treatment strategy might also boost the efficacy and reduce resistance to available anti-cancer drugs and so-called anti-angiogenic drugs that work by cutting off the growth of new blood vessels.

"In tumors, the endothelial cells lining blood vessels grow in all directions and over each other," said Peter Carmeliet of Vesalius Research Center. Irregular shape and gaps left in the vessel walls also make them leaky.

Tissues need oxygen delivered by the bloodstream to grow. But, in the case of tumors, that haphazard overgrowth of blood vessels and deteriorated endothelial lining impairs their own ability to function, he continued. As a result, tumors become more and more oxygen deprived – a condition that is a "driving force" for cancer cells to escape and spread to other parts of the body.

That vicious cycle might be halted with treatments designed to target an oxygen-sensing enzyme known as PHD2 in the linings of tumors' blood vessels, Carmeliet's team now finds. The new results also offer fundamental new insight into blood vessel biology.

Indeed, numerous earlier studies had examined how blood vessels arise, branch and elongate at the molecular level. However, little was known about how vessels regulate their shape.

Since supply of oxygen is one of the most basic functions of vessels, the researchers also suspected that they should possess ways to sense and re-adapt oxygen supply in the case of a shortage. They looked to a newly discovered class of oxygen sensors: the prolyl hydroxylase domain proteins, PHD1-3.

In the current study, Carmeliet's group focused on the role of PHD2 in balancing oxygen levels by influencing the characteristics of blood vessels. In mice with half the normal amount of PHD2 in the endothelial cells that line blood vessels, tumor vessels were found in the same numbers and sizes. However, the shape and structure of those vessels was more "normal," with linings made up of tightly aligned, orderly shaped and smooth cells having a cobblestone appearance.

That more regular vessel structure improved tumors' oxygen supply, leading to physiological changes that counteracted the overall malignancy of the cancer, they report. The cells were better able to counterbalance the "abnormalizing" effects of the tumors, and halt the progression to metastasis.

The findings in mice may have medical implications. "By normalizing the tumor vasculature, partial loss of PHD2 may shift tumors from an aggressive metastasizing tumor type to a more benign, well-encapsulated tumor," the researchers said. The partial loss of PHD2 doesn't seem to affect the blood vessels of healthy tissues, they said, suggesting a PHD2 inhibitor might selectively target tumor vessels.

Working to keep a tumor well-supplied with a key nutrient like oxygen may seem counterintuitive, but such a therapy might also be an advantageous addition to existing treatment regimens, Carmeliet added, noting that chemotherapeutic drugs and radiation depend on adequate oxygen levels to work. Targeting PHD2 might also help to avoid a potential pitfall of anti-angiogenic drugs that attempt to "starve" tumors by pruning back their blood vessel supply. "You have to be careful," he said. "If you prune too many vessels, leaving tumors overly hypoxic, it may induce their resistance."

This research might also open new methods of treatment for disorders that are accompanied by a shortage of oxygen, such as myocardial infarction or stroke. The researchers also hope to be able to use this discovery to tackle the morbid growth of blood vessels in the retina.

This research was purblished online on February 12th in the journal Cell.


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Cite This Page:

Cell Press. "'Normalizing' Tumor Vessels Leaves Cancer More Benign." ScienceDaily. ScienceDaily, 21 February 2009. <www.sciencedaily.com/releases/2009/02/090212125126.htm>.
Cell Press. (2009, February 21). 'Normalizing' Tumor Vessels Leaves Cancer More Benign. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2009/02/090212125126.htm
Cell Press. "'Normalizing' Tumor Vessels Leaves Cancer More Benign." ScienceDaily. www.sciencedaily.com/releases/2009/02/090212125126.htm (accessed October 20, 2014).

Share This



More Health & Medicine News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How Nigeria Beat Its Ebola Outbreak

How Nigeria Beat Its Ebola Outbreak

Newsy (Oct. 20, 2014) The World Health Organization has declared Nigeria free of Ebola. Health experts credit a bit of luck and the government's initial response. Video provided by Newsy
Powered by NewsLook.com
Another Study Suggests Viagra Is Good For The Heart

Another Study Suggests Viagra Is Good For The Heart

Newsy (Oct. 20, 2014) An ingredient in erectile-dysfunction medications such as Viagra could improve heart function. Perhaps not surprising, given Viagra's history. Video provided by Newsy
Powered by NewsLook.com
Ebola Worries End for Dozens on U.S. Watch Lists

Ebola Worries End for Dozens on U.S. Watch Lists

Reuters - US Online Video (Oct. 20, 2014) Forty-three people who had contact with Thomas Eric Duncan, the first person diagnosed with Ebola in the U.S., were cleared overnight of twice-daily monitoring after 21 days of showing no symptoms. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Fauci: Ebola Protocols to Focus on Training

Fauci: Ebola Protocols to Focus on Training

AP (Oct. 20, 2014) Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, says he expects revised CDC protocols on Ebola to focus on training, observation and ensuring health care workers are more protected. (Oct. 20) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins