Cell Ageing May Increase Spread of Ovarian Cancer Which Is Undetected Until It Metastasizes Beyond the Ovary

Ageing in cells is a factor in the spread of cancer. Researchers from the Indian Institute of Science (IISc) in Bengaluru discovered that cancer cells settle down on aged tissues.

Ovarian Cancer Cell Settle in Ageing Tissues

In a recent study, scientists have discovered that ovarian cancer cells proliferate more readily in senescent or old tissues because these tissues release a distinct extracellular matrix that draws the cancer cells that are spreading.

The researchers employed a senescent model produced by chemotherapy to investigate this phenomenon. First, they removed tissues from mice models that were found lining internal cavities, and they exposed half of these tissues to cancer-treating chemotherapy, causing them to enter a state known as senescence, in which the cells cease to divide but do not perish.

"In a cell or tissue, what you might call ageing in a body, you would call senescence," stated Associate Professor Ramray Bhat of the Department of Developmental Biology and Genetics (DBG).

Then, the scientists exposed human tissue-like cell sheets and young and old mouse tissues to ovarian cancer cells. The normal and malignant cells were labeled with distinct fluorescent markers using time-lapse imaging, allowing for prolonged microscopic observation.

They discovered that the cancer cells concentrated more on the aging tissues. Additionally, they migrated toward the older, normal cells in the cell sheets.

The team initially questioned if the cancer cells were drawn to signaling molecules that the old cells released and diffused over vast distances to determine what attracted them to the aged cells. They constructed computer models to investigate the connections between the cancer cells and the old cells.

It was unexpected for the researchers to discover that the diffusing chemicals were not attracting the cancer cells. The cancer cells were being called by proteins released by old cells that become the extracellular matrix (ECM), the substrate upon which the cells cling and proliferate.

"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 group conducted studies on human cell lines to verify the computer simulations' predictions. It was seen that the cancer cells adhered tenaciously to the extracellular matrix surrounding the old cells, gradually eliminating the old cells. Additionally, they observed that the cancer cells could adhere more firmly because the aged ECM had higher amounts of proteins, including fibronectin, laminin, and hyaluronan, than the ECM of the young cells.

The researchers speculate that this may be one of the causes of older people's generally worse cancer outcomes compared to younger groups based on their findings.

Chemotherapy Induces Senescence

Chemotherapy is one of the very popular cancer treatments. However, it can also induce senescence or aging of tissues.

Chemotherapy induces senescence in an attempt to stop cancer cells from proliferating. Recent investigations with transformed cells have demonstrated that this reaction is not always definitive and that persistent populations can use senescence as an adaptive route to resume proliferation and grow more aggressive.

Prof. Bhat confirmed this, noting that "senescence can make things worse." She suggested using chemotherapy appropriately to get satisfying outcomes for ovarian cancer.

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