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Tuesday, August 23, 2016
TAU: Groundbreaking Cancer Research

Groundbreaking research: Tel Aviv University researchers together with the
German Cancer Research Center (DKFZ) in Heidelberg, discover the mechanism
by which melanoma spreads to other organs in the body, and find ways to
prevent the metastasis

Research leader Dr. Carmit Levy: "We hope that our findings will help turn
melanoma into a nonthreatening, easily curable disease."

The paper was published yesterday (Monday 22 August 2016), as the leading
cover-page article of the prominent scientific journal Nature Cell Biology.

For link to the journal article:
http://www.nature.com/ncb/journal/vaop/ncurrent/full/ncb3399.html


GPO News 23 August 2016

In a landmark discovery, researchers at Tel Aviv University have unraveled
the metastatic mechanism of melanoma, the most aggressive of all skin
cancers. The scientists discovered that before spreading to other organs,
the tumor sends out tiny vesicles containing molecules of microRNA. These
induce morphological changes in the dermis – in preparation for receiving
and transporting the cancer cells. The researchers also found chemical
substances that can stop the process, and are therefore promising drug
candidates.

The paper was published yesterday (Monday, 22 August 2016) as the leading
cover-page article of the prominent scientific journal Nature Cell Biology.

Melanoma, the most aggressive and lethal type of skin cancer, causes the
death of one person every 52 minutes (according to data from the Skin Cancer
Foundation), and the number of diagnosed cases has been on the rise for the
past three decades. Despite a range of therapies developed over the years,
there is still no full remedy for this life-threatening disease. A recent
study at Tel Aviv University proposes new and effective methods for
diagnosing and preventing this most deadly of skin cancers.

"The threat of melanoma is not in the initial tumor that appears on the
skin, but rather in its metastasis – cancer cells sent off to colonize in
vital organs like the brain, lungs, liver and bones," says research leader
Dr. Carmit Levy of the Department of Human Molecular Genetics and
Biochemistry at Tel Aviv University's Sackler School of Medicine. "We
discovered how the cancer spreads to distant organs, and found ways to stop
the process before the metastatic stage."

Morphological changes in the dermis

The researchers began by examining pathology samples taken from melanoma
patients, and the findings were striking indeed. "We looked at samples of
early melanoma, before the invasive stage," says Dr. Levy. "To our surprise
we found changes that had never before been reported, in the morphology of
the dermis – the inner layer of the skin. Our next task was to find out what
these changes were, and how they related to melanoma." In the ensuing long
and complex study the group was able to discover - and also block – a
central mechanism in the metastasis of melanoma.

According to Dr. Levy, scientists have known for years that melanoma forms
in the outer layer of the skin, the epidermis. At this early stage the
cancer is unable to send off colonizing cancer cells, because it has no
access to blood vessels - the highways that carry the cells to other parts
of the body. With no blood vessels present in the epidermis, the tumor first
needs to contact the abundant blood vessels running through the dermis. But
how is the connection made?

"We found that even before the cancer itself invades the dermis, it sends
out tiny vesicles containing molecules of microRNA. These induce the
morphological changes in the dermis, in preparation for receiving and
transporting the cancer cells. It now became clear to us that by blocking
the vesicles, we may be able to stop the disease altogether."

Transforming melanoma into a nonthreatening illness

Having discovered the mechanism, the researchers proceeded to look for
substances that could intervene and block the process in its earliest
stages. They found two such chemicals: one (SB202190( inhibits the delivery
of the vesicles from the melanoma tumor to the dermis; and the other (U0126)
prevents the morphological changes in the dermis even after the arrival of
the vesicles. Both substances were tested successfully in the lab, and may
serve as promising candidates for future drugs. In addition, the changes in
the dermis, as well as the vesicles themselves, can be used as powerful
indicators for early diagnosis of melanoma.

"Our study is an important step on the road to a full remedy for the
deadliest skin cancer," says Dr. Levy. "We hope that our findings will help
turn melanoma into a nonthreatening, easily curable disease."

The group at Tel Aviv University worked in close collaboration with Prof.
Jörg D. Hoheisel and Laureen Sander at the German Cancer Research Center
(DKFZ) in Heidelberg, Dr. Shoshi Greenberger at the Sheba Medical Center and
Dr. Ronen Brenner at the Wolfson Medical Center in Holon. Lab research was
led by Dr. Shani Dror of Dr. Levy's research group.

(The research was funded with the support of the Science, Technology and
Space Ministry in the framework of a joint German-Israeli cancer research
program.)

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