Schepens scientists are first to discover angiogenesis switch inside blood vessel cells

May 18, 2006

Boston, MA--Scientists at Schepens Eye Research Institute, an affiliate of Harvard Medical School, are the first to discover a switch inside blood vessel cells that controls angiogenesis (new blood vessel growth). The switch, they learned, is turned on and off by the balance between two enzymes (known as PI3K and PLCg) that compete for the use of the same lipid membrane to fulfill opposite missions, growth and regression, respectively. This finding could lead to new, more targeted drugs for diseases such as cancer, diabetic retinopathy and macular degeneration. The study, titled "Regulating angiogenesis at the level of PtdIns-4,5P2," is published in the current issue of The EMBO Journal (May 17).

"This is a significant discovery that holds great promise for future treatments," says principal investigator and senior Schepens scientist, Dr. Andrius Kazlauskas, who adds that scientists have long suspected an "intracellular" switching process, but until now have known very little about it. "Current drugs focus on suppressing angiogenesis by inhibiting a mechanism outside the vessel cells, which involves the action of growth factors such as VEGF or vascular endothelial growth factor. While effective in preventing vessel growth, these drugs have little impact on existing, stable vessels," he says. "Our discovery may help design drugs that could dismantle existing vessels by targeting this switch inside the vessel cells."

Angiogenesis is an important natural process that can be both good and bad for the body. It restores blood flow after injury, prepares a woman's body for pregnancy and increases circulation in a damaged heart. But, it can also nourish cancer tumors and damage delicate retinal tissues when uncontrolled.

The angiogenic process is triggered by what the body perceives as a need for additional blood flow. In the case of disease, it is a mistaken need. In response, the body sends growth factors (such as VEGF) to blood vessels in the "needy area" to bind to receptors on the surface of the endothelial cells. This binding then sets off a series of signaling activities carried out by enzymes within the cells. Two of those enzymes are PI3K and PLCg, which then search for their favorite lipid to use in their respective missions. Until the present study, scientists did not know exactly what those missions were and how they were accomplished.

Kazlauskas and his team were determined to answer those questions. To do so they created laboratory conditions that would allow them to observe the two enzymes separately as they acted on the lipid. In a series of "in vitro" or laboratory experiments that controlled the presence of each enzyme, they began to understand the individual roles of those enzymes.

The research team discovered the following. When the PI3K enzyme acts on the lipid, it converts it (the lipid) into a modified form of itself, which then signals blood vessel cells to proliferate or grow. The team also found that when PLCg acts on the lipid, it cuts the lipid in two, thus preventing PI3K from using that very same lipid to promote vessel growth. Instead, they learned, the resulting two halves of the lipid trigger a series of signaling activities that caused vessels to regress and disappear.

The team concluded that it was the competitive relationship between these two enzymes for the lipid that was at least part of the intracellular switch for which they and other scientists have been searching. They also concluded that blood vessel growth or regression was dependent on the relative activity of the two enzymes and on the amount of the lipid within the endothelial cells.

"Understanding this process opens a whole new avenue for treatment of angiogenesis-related diseases," says Kazlauskas. "For instance, drugs could be designed to decrease PI3K in cancer patients or those with proliferative diabetic retinopathy or macular degeneration, or designed to increased it in a damaged heart," he says.

Next steps for the research team include identifying the signaling events by which PLCg informs the vessels to undergo regression and the molecules that execute the regression command.
-end-
Schepens Eye Research Institute, an affiliate of Harvard Medical School, is the largest independent eye institute in the world.

Harvard Medical School

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.