Suppressing the spread of tumors
Researchers discover a protein that suppresses tumor metastasis

Date:
February 8, 2022
Source:
Institute of Science and Technology Austria
Summary:
When tumors spread, cancer cells migrate to other parts of the body
through the blood or lymphatic vessels. Scientists have now found
a new protein that prevents cancer cells from doing so by making
them stick more tightly to their surroundings. Their findings
could in the future help doctors determine the aggressiveness of
a tumor and fine-tune the therapy.



FULL STORY ==========================================================================
Why some patients develop metastases and others do not is largely unclear.

Researchers around ISTA professor Daria Siekhaus are now contributing to
a better understanding of the process in certain types of cancer. They
took a close look at the role of a protein called MFSD1 -- the mammalian relative of a protein they had previously identified as affecting cell migration in fruit flies. Therefore, first author Marko Roblek from the Siekhaus group created mouse cancer cells lacking the protein. Without
the protein, cells traveled much faster, suggesting that MFSD1 prevents
the cells from moving. Together with collaborators from the University of Zurich, the team tested their theory in living mice with breast, colon,
and skin cancer. "In the absence of MFSD1, there was a strong increase
in metastasis," Daria Siekhaus summarizes the results.


========================================================================== Cancer cells resist starvation and stress "We wanted to know why lower
MFSD1 levels were beneficial to the tumor apart from allowing them to
move more freely. As cancer cells travel through the blood for example,
they experience a lot of mechanical stress," Marko Roblek explains. Thus,
the researchers performed a stress test on cancer cells with and without
the protein. Using a tiny rubber scraper, Roblek tried to scrape the cells
off the surface of the Petri dish in which he had grown them. While the
cancer cells containing MFSD1 quickly died under the mechanical stress,
those without the protein tended to remain intact. Without the protein,
the team concluded, certain tumor cells could more easily enter the
bloodstream and find their way to other parts of the body. In another experiment, the researcher tested the cancer cell's resistance to nutrient starvation with a similar result. Again, the cells lacking MFSD1 survived
for longer.

Protein prevents detachment The team was able to show that both the
cell's reaction to starvation and mechanical stress are caused by the
protein MFSD1. It does so by affecting specific receptors located at the
cell surface. These so called integrins ensure the cells stick to each
other and the extracellular matrix, a dens network surrounding the cells
in our body. In a constant circle, the cell produces these receptors, transports them to the cell surface and back inside the cell. If a tumor
cell lacks MFSD1, they fail to recycle a certain type of integrin. "The
result is, that the cells stick less to the surrounding tissue and each
other, which makes it easier for them to migrate," says Daria Siekhaus.

Patient data supports findings The team's findings are also supported by
an analysis of patient data by Rita Seebo"ck from the University Hospital
St. Po"lten, Austria. The data, which is available online to researchers
in anonymized form, showed a correlation between the level of MFSD1 and
the patient's prognosis. "We've seen that patients suffering from specific forms of breast, gastric and lung cancer who had lower levels of MFSD1 had
a worse outcome. A high level of MFSD1 seems to be protective -- it works
like a suppressor of tumor metastasis," cancer researcher Roblek says.

To optimize therapy for their patients, doctors are already analyzing
the expression of certain genes. Now, they can also look for the gene
encoding the protein MFSD1. "If this marker becomes more established,
doctors can use it to help classify how aggressive the cancer is and to
decide between different treatment options," suggests biologist Daria
Siekhaus. In future studies, the team wants to focus in detail on how
the protein functions on a molecular level and is curious to learn if artificially raising the amount of MFSD1 could help suppress the spread
of certain tumors. The long term goal is to examine if it can be used
as a therapeutic target.

========================================================================== Story Source: Materials provided by Institute_of_Science_and_Technology_Austria. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Marko Roblek, Julia Bicher, Merel van Gogh, Attila Gyo"rgy, Rita
Seebo"ck, Bozena Szulc, Markus Damme, Mariusz Olczak, Lubor Borsig,
Daria E. Siekhaus. The Solute Carrier MFSD1 Decreases the Activation
Status of b1 Integrin and Thus Tumor Metastasis. Frontiers in
Oncology, 2022; 12 DOI: 10.3389/fonc.2022.777634 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220208085014.htm
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