Mystery of cancer spread found in Nature sub-journal

In a living embryo, the back end of a moving cell population propels the cell population forward, a new study published Feb.
14 in Nature Cell Biology finds
.

This is in contrast to previous research, which found that a population of cells growing in a petri dish pushes itself forward with the front end

The study, led by researchers at NYU Grossman School of Medicine and the NYU Courant Institute for Mathematical Sciences, used a new technique to measure when cell populations move along tissue membranes and into position in developing animals.
applied force
.

Specifically, the study found for the first time in animal tissues that as they moved forward, a protein called integrin on the surface of cells in the back was more attached to the cell membrane than cells in the front, and moved in one direction Apply more force

Confirmation of this mechanistic detail in living tissue is of great importance, as many cancers spread in cell populations and may use the newly discovered "back engine propulsion," the researchers said
.

"Our findings shed light on how the populations of cells that will become organs move into place and reiterate that cells behave differently when they leave their natural environment," said senior study author, NYU Langone said Dr.
Holger Knaut, associate professor in the Department of Cell Biology in the School of Health
.

Research details

These findings are based on cell motility mechanisms established by previous studies
.

For example, a protein called actin is thought to form a cell's protein "skeleton," with chains of actin able to grow in specific directions and exert forces to change the cell's shape

The new study examined the movement of cell populations in zebrafish embryos
.

The zebrafish embryo is a prime model for developmental studies because it shares many of the same cellular mechanisms as human cells, and because the zebrafish embryo develops externally, each stage of development can be directly observed with high-power microscopy

"In this type of research, we combine advanced microscopy techniques with automated, high-throughput computational models to measure cellular forces in living tissue," said Daniele Panozzo, Ph.
D.
, associate professor at NYU's Courant Institute for Mathematical Sciences
.

Using the "bleached" spots of the basement membrane to measure shape changes over a minute, and a new software called embryogram to calculate how far the spots moved in the basement membrane, the researchers determined how many cells and pushed and pulled the membrane, "like a tire on the road
.

" This The effect is much like a high school physics experiment, in which students draw two points on a rubber band, then measure the change in distance between the points to calculate the force they apply as they stretch the rubber band

Armed with these tools, the team found that primordial cells connect the force-producing actin-myosin network at the back end of the mobile group through clusters of integrins on the side close to the basement membrane
.

The team's theory is that cells attached to the cell membrane push the cells in front of them backwards, moving the entire population

Interestingly, the study found that the primordium moves in a "continuous breaststroke" fashion by pushing the basement membrane down, sideways and back, much like a swimmer's arm
.

The author has no idea why this is happening, but speculates that this is the most efficient way to move forward

The authors say this study shows that by designing treatments that block the action of integrins, swarm cell movement has the potential to be used to stop cancer from spreading
.

In clinical trials, integrin inhibitors have been tested as drugs to treat cardiovascular and autoimmune diseases, but their use to treat cancer spread has been limited due to the need to better understand their mechanisms

Journal Reference :

1. Naoya Yamaguchi, Ziyi Zhang, Teseo Schneider, Biran Wang, Daniele Panozzo, Holger Knaut.
   Rear traction forces drive adherent tissue migration in vivo .
   Nature Cell Biology , 2022; DOI: 10.
   1038/s41556-022-00844-9