A new study from Finland sheds
fresh light on how melanoma cells interact with other cells via extracellular
vesicles they secrete. The researchers found that extracellular vesicles
secreted by melanoma cells use the so-called hedgehog signalling pathway to
intensify the malignant properties of the cells they are targeting. The
discovery can help in the development of better treatment and diagnostics for
melanoma. Published in Cellular and Molecular Life Sciences,
the study was carried out in collaboration between researchers from the
University of Eastern Finland and the University of Helsinki.
Many of the
mechanisms regulating the function of our body have remained unchanged
throughout evolution. This means that the same genes regulate the development
and function of all multicellular animals. One example of such gene survival is
the so-called hedgehog signalling pathway. The gene family associated with this
signalling pathway gets its unique name from a mutation it caused in fruit fly
larvae, making them look spiky, just like a hedgehog. The most common of the
three hedgehog genes found in mammals, the Sonic hedgehog gene, was aptly named
after the famous video game character. In mammals, members of the hedgehog gene
family are essential regulators of foetal development, but they are also
associated with stem cell division in later stages of development and even in
adults. Recent studies suggest that their expression is also associated with
many different types of cancer, including skin cancers. Melanoma is the most
severe form of skin cancer, and it is becoming more and more common.
Extracellular
vesicles carry signals between cells – and they can also carry packaged drugs
Traditionally,
signalling in the body is thought to take place via freely circulating signals,
such growth factors and hormones. According to a more recent view, however, it
is believed that some signals are packaged for transportation to protect them
against breakage and to ensure their delivery to the correct address.
Extracellular vesicles are small, bubble-like packages made of cell membrane,
serving as natural carriers of signals in the body. They regulate the function
of the body already during the foetal stage, via breast milk and also later in
life as our tissue regenerates. Cancer cells, too, use extracellular vesicles
to deliver signals and to modify their environment, making it favourable to
growth. Extracellular vesicles can also be used as diverse carriers of drugs to
combat diseases and to repair tissue damage – and this is why they are being
studied so actively at the moment.
In the newly published
study, the researchers discovered a new link between extracellular vesicles and
hedgehog molecules. They found that vesicles secreted by melanoma cells
intensify the malignant properties of the cells they are targeting, such as
division and spreading, via the hedgehog signalling pathway. The researchers
used cultured human melanoma cells and normal skin cells, confirming their
findings from the cell culture by analysing tissue samples from patients with
melanoma.
“It is quite a
coincidence that these signal-carrying vesicles originate from cells that are
also known as hedgehog cells due to their microscopically small, spike-like
protrusions. These protrusions, however, don’t have anything to do with fruit
fly larvae; instead, they are typically found in cells that are active in
producing hyaluronan, the most common sugar molecule in the extracellular
matrix,” Docent Kirsi Rilla from the University of Eastern Finland says.
“Hyaluronan also
plays a key role in vesicle mediated signalling, as hyaluronan found on the
surface of vesicles protruding from the cell surface facilitates their binding
to the target cell.”
The hedgehog
signalling pathway holds great promise as a target for drug therapy in melanoma
and other cancers. The regulation mechanism now discovered by the researchers
can be made use of in the development of better diagnostics and drug therapy
for patients with melanoma.
Journal article: https://link.springer.com/article/10.1007%2Fs00018-019-03399-5
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