Ovarian cancer spreads easier in ageing cells: IISc study

Bengaluru: Researchers at the Indian Institute of Science (IISc) have found that ovarian cancer cells can spread more easily in aged tissues because it secretes a unique extracellular matrix that attracts the spreading cancer.

The researchers used a chemotherapy-induced model; they extracted tissues found in the lining of body cavities from mice models and exposed half of these tissues to chemotherapeutics used to treat cancer, pushing them to senescence — a state where cells stop replicating, but don’t die.

"What you might call ageing in a body, in a cell or tissue you would call it senescence,” Ramray Bhat, Associate Professor at the Department of Developmental Biology and Genetics and corresponding author of the study, said.

IISc said the team exposed both young and aged mouse tissues and human tissue-like cell sheets to ovarian cancer cells. They found that the cancer cells chose to settle down more on the aged tissues. In the cell sheets, they settled closer to the aged normal cells.

Deeper analyses threw up surprising results — it was the proteins secreted by aged cells and settled down as the extracellular matrix (ECM), the base on which the cells adhere and grow, that were attracting the cancer cells.

Bharat Thapa, a former biology undergraduate student at IISc, now pursuing a PhD at Vanderbilt University, USA, is the first author of the study that was published in the journal Cellular and Molecular Life Sciences.

The researchers 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. They suggested this could be one of the reasons why aged populations typically tend to have worse outcomes in cancer than younger populations.

Bhat noted that chemotherapy also induces senescence that can make things worse. “Appropriate use of chemotherapy could be very important in getting good outcomes in ovarian cancer,” he said.

Thapa hoped that future studies will build a strong case for using senolytics — drugs that kill senescent cells — as a combination therapy with chemotherapeutics to tackle cancer progression.