Essential protein for the formation of new blood vessels identified

January 17, 2012
Nascent cell-cell contacts between endothelial cells. The transmembrane protein VE-Cadherin (green) mediates the formation of cellular junctions and is connected to the intracellular actin cytoskleton (red). The nucleus is stained in blue. Credit: Reiner Wimmer

New research explains how cells regulate their bonds during the development of new blood vessels. For the first time, the role of the protein Raf-1 in determining the strength of the bond between cells has been shown. If Raf-1 is not present, the cells cannot stick together and the formation of new blood vessels is inhibited. This discovery may one day lead to new approaches to cancer treatment.

Angiogenic sprouting, the process by which new grow from existing vessels, is a double-edged sword. It enables the to develop in the embryo, and is vital for in adults. But it also supplies growing tumors with nutrients and oxygen.

is an example of collective cellular migration. Cells move as a group, held together by connections called adherens junctions. For the cells to move, they have to make and break these connections continuously. If the junctions are too stiff, they will not be able to move at all, but if they are too weak, the groups of cells will break apart. How this mechanism is controlled was unknown.

The video will load shortly
In vitro vessel formation of control and Raf-1 deficient endothelial cells. In the absence of Raf-1 cells are unable to migrate collectively and fail to form capillary like structures in 3D fibrin gels. Frames were taken every 30min and the movie is displayed at 15fps (Credit: Reiner Wimmer).

The mechanism has now been uncovered by Manuela Baccarini’s group at the Max F. Perutz Laboratories, a joint venture of the University of Vienna and the Medical University of Vienna, who investigate cell signaling. They have established a crucial role for Raf-1, a multi-purpose signal transducer, in this process.

“The real breakthrough came when we were able to use video microscopy on the developing vessels in vitro,” explains the paper’s first author Reiner Wimmer. “We realized that the cells without Raf-1 were actively migrating, but only as single cells. They could not migrate in a group.”

The video will load shortly
In vitro vessel formation of control and Raf-1 deficient endothelial cells. In the absence of Raf-1 cells are unable to migrate collectively and fail to form capillary like structures in 3D fibrin gels. Frames were taken every 30min and the movie is displayed at 15fps (Credit: Reiner Wimmer).

The meaning of this discovery became clear in further experiments: the role of Raf-1 is to bring the new adherens a kinase they need for the remodeling of the cytoskeleton. This means that Raf-1 is fine-tuning the bonds between the migrating cells by causing the local remodeling of the cell’s cytoskeleton.

As the process of angiogenic sprouting is necessary for the growth of tumors, this new discovery may one day be applied to produce cancer therapies to target Raf-1 and the other parts of this control mechanism, thereby disrupting the environment of the tumor.

Explore further: Researchers find surprising role for enzyme in tumor cell division and new drug to combat it

More information: Wimmer R, et al. (2011). Angiogenic sprouting requires the fine-tuning of endothelial cell cohesion by the Raf-1/Rok-α complex. Developmental Cell. DOI:10.1016/j.devcel.2011.11.012 , PMID: 22209329

Related Stories

Researchers gain new insights into how tumor cells are fed

August 8, 2011

Philadelphia, PA, August 8, 2011 – Researchers have gained a new understanding of the way in which growing tumors are fed and how this growth can be slowed via angiogenesis inhibitors that eliminate the blood supply ...

Recommended for you

Synthetic 3D-printed material helps bones regrow

September 28, 2016

A cheap and easy to make synthetic bone material has been shown to stimulate new bone growth when implanted in the spines of rats and a monkey's skull, researchers said Wednesday.

Epigenetic clock predicts life expectancy

September 28, 2016

UCLA geneticist Steve Horvath led a team of 65 scientists in seven countries to record age-related changes to human DNA, calculate biological age and estimate a person's lifespan. A higher biological age—regardless of chronological ...

Engineered blood vessels grow in lambs

September 27, 2016

In a hopeful development for children born with congenital heart defects, scientists said Tuesday they had built artificial blood vessels which grew unaided when implanted into lambs, right into adulthood.

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.