IISc study explains why older adults have worse cancer outcomes

New Delhi: Scientists at the Indian Institute of Science (IISc), Bengaluru, have found that cancer cells can spread more easily in tissues that are senescent or aged, a finding that may explain worse outcomes in the elderly patients than the young.

In the study, published in Cellular and Molecular Life Sciences, the team explained that the aged tissues secrete a unique protein called extracellular matrix -- the base on which the cells adhere and grow -- which lure the cancer cells.

To understand, the scientists used a chemotherapy-induced senescent model. 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) at IISc.

The team then exposed both young and aged mouse tissues and human tissue-like cell sheets to ovarian cancer cells.

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.

They found 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. Surprisingly, they found it was not the diffusing molecules that were luring the cancer cells, but ECM.

“The extracellular matrix is what was bringing the cancer cells there and allowing them to better attach near the aged cells and spread faster,” Bhat said.

Further experiments on human cell lines revealed that the cancer cells stuck strongly to the ECM 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,” Bhat said. “Appropriate use of chemotherapy could be very important in getting good outcomes in ovarian cancer.”

One way forward could be to focus on finding probes that can identify some of these matrix proteins, which can help predict where the cancer cells would get deposited in the tissues, Bhat said. The team also hoped that future studies will focus on using senolytics -- drugs that kill senescent cells -- as a combination therapy with chemotherapeutics to tackle cancer progression.