Key to why melanoma is so potent Posted Sunday, September 4, 2005 by arjuna
http://news.bbc.co.uk/1/hi/health/4207340.stm
BBC NEWS
* Scientists have discovered why a form of skin cancer called melanoma
can be so malignant. *
If not caught early the disease can spread through the body with an
efficiency few other tumours possess.
Latest research suggests that, unlike other cancer cells, melanoma does
not have to learn how to spread - it has that ability innately.
The research, by Whitehead Institute for Biomedical Research in the US,
is published in Nature Genetics.
*Certain embryonic genes normally involved in transferring cells from
one part of the body to another are also involved in enabling cancer
cells to spread *
Professor Robert Weinberg,
Lead researcher
Lead researcher Professor Robert Weinberg said: "Other cancers need to
learn how to spread, but not melanoma.
"Now, for the first time, we understand the genetic mechanism
responsible for this."
The spread of disease to an unconnected body part - known as metastasis
- is a highly inefficient, multi-step process that requires cancer cells
to jump through many hoops.
* Slug gene *
The cells first must invade a nearby tissue, then make their way into
the blood or lymphatic vessels.
Next they must migrate through the bloodstream to a distant site, exit
the bloodstream, and establish new colonies.
Researchers have wondered why melanoma in particular is able to do this
not only more efficiently than other cancers, but at a far earlier stage.
The latest study shows that as melanocytes - cells that protect the skin
from sun damage by producing pigmentation - morph into cancer cells,
they immediately reawaken a dormant cellular process that lets them
travel swiftly throughout the body.
Central to this reawakened process is a gene called Slug which plays a
key role in allowing cells to travel around the developing embryo in the
womb.
Normally the gene is shut off in adult tissues, but the researchers
found that when skin cells become malignant they reactivate Slug, and
thus immediately acquire the ability to spread.
* Injected cells *
The researchers injected cancer-causing genes into normal human cells
and then injected the resulting tumours under the skin of mice.
Mice injected with breast or connective tissue cancer cells developed
tumours - but these did not spread.
* It is also important to remember that the vast majority of melanomas
are caused by UV damage from excess sun exposure *
Dr Julie Sharp,
Cancer Research UK
But those injected with melanoma cells immediately developed invasive
tumours throughout their body.
Detailed analysis showed that Slug was expressed in the melanoma cells.
When the gene was knocked out in melanoma cells, the cancer was unable
to spread when introduced into a mouse.
Professor Weinberg said: "This work is a demonstration of the notion
that certain embryonic genes normally involved in transferring cells
from one part of the body to another are also involved in enabling
cancer cells to spread."
The same team last year showed a similar embryonic gene, Twist, played a
role in the spread of certain forms of breast cancer.
Dr Julie Sharp, senior cancer information officer at Cancer Research UK,
said: "If scientists can target treatments to block the Slug gene, they
might be able to prevent cancer spread and improve survival from this
disease in the future," she said.
"It is also important to remember that the vast majority of melanomas
are caused by UV damage from excess sun exposure."