Researchers at the Bengaluru-based Indian Institute of Science (IISc) have found that ovarian cancer cells can spread more easily in tissues that are aged because these tissues secrete a unique extracellular matrix that attracts the spreading cancer.
The discovery holds importance as ovarian cancer is dangerous as it often goes undetected until it has spread beyond the ovaries, and the symptoms can also be attributed to other conditions.
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 at the Department of Developmental Biology and Genetics (DBG) and corresponding author of the study published in 'Cellular and Molecular Life Sciences'.
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.
“It's slightly harder to image tissues when compared to cell lines as the latter has only one particular cell type growing,” added Bharat Thapa, first author and former biology undergraduate student at IISc. 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.
The team also 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,” says Bhat. “Appropriate use of chemotherapy could be very important in getting good outcomes in ovarian cancer.”
