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The distribution of attention of blood vessels

The institute's scientists discovered that the blood vessels "separate" between cell division and splitting in new directions. The findings imply that chemotherapy treatments may encourage the growth of blood vessels in the tumor

Growing blood vessels (white arrows) in a zebrafish embryo, under a microscope. The wall cells (red) express a gene (yellow) that blocks the division of cells that are in the midst of the process of sprouting and dividing from the main blood vessel (blue arrows)
Growing blood vessels (white arrows) in a zebrafish embryo, under a microscope. The wall cells (red) express a gene (yellow) that blocks the division of cells that are in the midst of the process of sprouting and dividing from the main blood vessel (blue arrows)

Our blood vessels are multitasking champions. When they grow, the cells in their walls divide, and at the same time they undergo a specialization that will eventually make them part of the system of arteries, veins, or lymphatic vessels - and they also sprout, that is, they split in new directions. Prof. Radiation will yield and her group at the Weizmann Institute of Science set out to discover how these cells keep so many balls in the air, and got Surprising answers which may shed new light on cancer treatments, on the regeneration of heart tissue and on other medical conditions involving the growth of blood vessels.

Dr. Ayelet Jarfi-Vider, a former research student in Prof. Yaniv's laboratory in the Department of Biological Control, together with Dr. Ivan Bassi, Nega Moshe and Yaara Tabet, followed cell division in blood vessel walls in transparent embryos of zebrafish. To this end, they genetically engineered the fish so that the cell nuclei on the inner wall of their blood vessels and lymph vessels glow in different colors: green when the cell is dividing and red when it is in a "resting" state. The scientists were surprised to find that in cells that germinate to produce new blood vessels, the nucleus remains red. In other words, despite the excellent division of attention and the ability to juggle between tasks, the division of the cells was temporarily stopped - probably in order not to confuse the cell while it was in motion; Only when the cell has reached its destination, its nucleus turns green, meaning it divides again.

Stopping cell division

Another surprise awaited the scientists when they tested which genes regulated the growth of blood vessels. As expected, they found a significant involvement of a growth factor called VEGFC which is prominently expressed when the cells begin to germinate and move. But this growth factor led to the expression of additional genes that inhibited cell division, including the well-known tumor suppressor p53; With the decrease in VEGFC levels, and consequently also in p53 levels, the cell returns to dividing. The p53 gene, also known as the "guardian of the genome", has been widely studied in the context of cancer, but the current study reveals a completely new role for it: to enable the proliferation of cells during the growth of blood vessels.

"We discovered a beautiful mechanism - the same growth factor that encourages blood vessel sprouting temporarily blocks cell division, so that the cell can germinate and move without bothering itself with division, a complex and demanding process in itself," explains Prof. Yaniv.

blood vessel. Illustration: depositphotos.com
blood vessel. Illustration: depositphotos.com

Later, the scientists blocked the cell division artificially using chemical inhibitors - some of which are also used to treat cancer. The result obtained was amazing: the blood vessels showed increased growth and the cells germinated in a disorderly manner without undergoing specialization into different types. The tangle of blood vessels that was formed was reminiscent of the blood vessels that often grow around and penetrate cancerous tumors. "It is possible that certain chemotherapy drugs solve one problem - that is, they stop the division of cancer cells - but create another problem: they encourage the growth of blood vessels that may help the survival of the tumor," says Prof. Yaniv.

A better understanding of the mechanisms of blood vessel growth is not only important for cancer treatment, but may also help to strengthen this growth in situations where tissue regeneration or revitalization is needed, for example, after a heart attack or stroke.

Dr. Gideon Chen from the Department of Biological Control of the Institute and Daniel Splichtuser, Dr. Masahiro Shin and Prof. Nathan Lawson from the University of Massachusetts Medical School also participated in the study.