New mechanism explains how the body prevents formation of blood vessels

November 11, 2009

Researchers at Uppsala University, in collaboration with colleagues in Sweden and abroad, have identified an entirely new mechanism by which a specific protein in the body inhibits formation of new blood vessels. Inhibiting the formation of new blood vessels is an important aspect of, for example, cancer treatment. The study is published in the November issue of the journal Molecular Cancer Research.

Angiogenesis, the formation of new blood vessels, is strictly regulated by a number of molecules that serve to either promote or inhibit the process. Certain diseases are characterised by excessive or insufficient angiogenesis. The rapid growth of tumors, for example, is conditioned on the formation of new blood vessels to supply oxygen and nutrients, which explains why angiogenesis is accelerated in cancer patients.

"At present, there are five approved drugs for inhibiting formation of new blood vessels," says research fellow Anna-Karin Olsson of the Department of Medical Biochemistry and Microbiology at Uppsala University, who headed the study. "All of these medications work in a similar way, by influencing the function of one of the agents that promotes angiogenesis. A problem with the medications is that the body develops resistance to them as treatment progresses. Improved knowledge about which molecules promote or inhibit the formation of blood vessels in the body, and the mechanisms by which they operate, is accordingly a research goal."

The study in question involved researchers from Uppsala University collaborating with colleagues in Sweden, Norway, Finland and Germany to investigate the function of histidine-rich glycoprotein (HRG), a plasma protein naturally present in the body. Previous studies involving mice had shown that HRG inhibits angiogenesis and tumor growth. The new study demonstrates, among other things, that the HRG fragment responsible for the inhibitory effect is present in human tissue, which suggests that it serves as one of the body's own angiogenesis inhibitors.

The HRG fragment in question inhibits angiogenesis by binding to endothelial cells, which participate in the formation of blood vessels. Analysis of a large number of human tissue samples allowed the researchers to determine that the HRG fragment binds to blood vessels in cancer patients but not in healthy persons. The study also showed that the HRG fragment binds to blood vessels in the presence of activated platelets, blood cells that limit bleeding in the event of injury. This finding is interesting in view of the fact that cancer patients often exhibit high levels of platelet activation.

"Our findings suggest that attempting to inhibit angiogenesis is an aspect of the body's own reaction to diseases like cancer," says Anna-Karin Olsson. "The activated platelets create a microenvironment in which the HRG fragment is able to function as an angiogenesis inhibitor."

Data from so-called "knockout" mice, which lack HRG, support this conclusion. The mice are healthy and fertile, but exhibit high levels of angiogenesis in connection with tumor growth. This finding is consistent with the hypothesis that the mice lack an angiogenesis inhibitor.

"Our data describes an entirely new mechanism of action for an endogenous angiogenesis inhibitor," says Anna-Karin Olsson. "This knowledge may eventually help in developing new, more effective drugs for inhibiting angiogenesis during disease treatment without affecting healthy vessels."
-end-


Uppsala University

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.