What you might call in a body ageing, in a cell or tissue, you would call
it senescence. According to the researchers, chemotherapy also induces
senescence, and that senescence can make things worse
A study by researchers at the Indian Institute of Science (IISc.) in
Bengaluru has revealed that ageing in cells can increase the spread of ovarian
cancer.
According to the IISc., ovarian cancer is dangerous because it often
goes undetected until it has spread beyond the ovaries, and the symptoms can
also be attributed to other conditions. Scientists believe that ageing can
increase the spread of ovarian and other cancers, but the underlying mechanisms
are not fully clear. Now, researchers have found that ovarian cancer cells can
spread more easily in tissues that are senescent, or aged, because these
tissues secrete a unique extracellular matrix that attracts the spreading
cancer.
The researchers used a chemotherapy-induced senescent model to study
this phenomenon. They first extracted tissues found in the lining of body
cavities from mice models and exposed half of these tissues to
chemotherapeutics that are used to treat cancer, pushing them to senescence – a
state in which the cells stop replicating, but don’t die.
“What you might call in a body ageing, in a cell or tissue, you would
call it senescence,” said Ramray Bhat, Associate Professor, Department of
Developmental Biology and Genetics (DBG).
nostic and treatment. | Photo Credit: Illustration by
Madhumitha S
A study by researchers at the Indian
Institute of Science (IISc.) in Bengaluru has revealed that ageing in cells can
increase the spread of ovarian cancer.
According to the IISc., ovarian cancer is
dangerous because it often goes undetected until it has spread beyond the
ovaries, and the symptoms can also be attributed to other conditions.
Scientists believe that ageing can increase the spread of ovarian and other
cancers, but the underlying mechanisms are not fully clear. Now, researchers
have found that ovarian cancer cells can spread more easily in tissues that are
senescent, or aged, because these tissues secrete a unique extracellular matrix
that attracts the spreading cancer.
The researchers used a chemotherapy-induced
senescent model to study this phenomenon. They first extracted tissues found in
the lining of body cavities from mice models and exposed half of these tissues
to chemotherapeutics that are used to treat cancer, pushing them to senescence
– a state in which the cells stop replicating, but don’t die.
“What you might call in a body ageing, in a
cell or tissue, you would call it senescence,” said Ramray Bhat, Associate
Professor, Department of Developmental Biology and Genetics (DBG).
The team then exposed both young and aged
mouse tissues and human tissue-like cell sheets to ovarian cancer cells. They
used time-lapse imaging to tag the normal and cancer cells with different
fluorescent markers so that they could be studied under a microscope for
extended periods of time.
What they found was that the cancer cells
chose to settle down more on the aged tissues. Moreover, they settled closer to
the aged normal cells in the cell sheets.
To figure out what was drawing the cancer
cells to the aged cells, the team first wondered if they were being attracted
to signaling molecules that were being secreted by the aged cells and diffusing
over long distances. They built computer models to explore the interactions
between the cancer cells and the aged cells.
What the researchers found was surprising, as
it was not the diffusing molecules that were luring the cancer cells. It was
proteins secreted by aged cells that settle down as the extracellular matrix (ECM)
– the base on which the cells adhere and grow – that were calling the cancer
cells.
“The ECM is what was bringing the cancer
cells there and allowing them to better attach near the aged cells and spread
faster,” said Prof. Bhat.
The team carried out experiments on human
cell lines to replicate the predictions of the computer simulations. They
noticed that the cancer cells stuck strongly to the extracellular matrix around
the aged cells, and eventually cleared the aged cells away. They also noticed
that the aged ECM had higher levels of proteins, such as fibronectin, laminin
and hyaluronan, compared to the young cells’ ECM, which allowed the cancer
cells to bind more strongly.
Based on their findings, the researchers
suggest that this could potentially be one of the reasons why aged populations
typically tend to have worse outcomes in cancer than younger populations.
“The fact is that chemotherapy also induces
senescence, and that senescence can make things worse. Appropriate use of
chemotherapy could be very important in getting good outcomes in ovarian
cancer,” said Prof. Bhat.
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