Researchers discover mechanisms behind spread of ovarian cancer in ageing cells
New Delhi, January 17
Proteins secreted by ageing tissues could be attracting ovarian cancer cells, helping them spread more easily, research has found.
Exposing young and aged tissues to ovarian cancer cells, the researchers at the Indian Institute of Science, Bengaluru, observed that the cancer cells chose to settle down more on the aged tissues.
They found that the ageing cells and tissues were releasing proteins that settle down as the extracellular matrix (ECM) – the base on which the cells adhere and grow – that were calling the cancer cells.
The researchers said this might be why aged population typically tends to have worse outcomes in cancer than younger populations.
“The fact is that chemotherapy also induces senescence (ageing), and that senescence can make things worse,” said Ramray Bhat, Associate Professor at the Department of Developmental Biology and Genetics and corresponding author of the study published in Cellular and Molecular Life Sciences.
While scientists believe that ageing can increase the spread of ovarian and other cancers, the underlying mechanisms were not fully clear, the researchers said.
For the study, the team first extracted tissues forming the lining of body cavities from mice models and induced senescence by exposing half of these tissues to chemotherapeutics used in treating cancer. Senescence is a state in which the cells stop replicating, but don’t die.
They then exposed both young and aged mouse tissues and human tissue-like cell sheets to ovarian cancer cells and studied them under a microscope.
“What you might call in a body ageing, in a cell or tissue you would call it senescence,” said Bhat.
Using computer modelling to understand the interactions between the cancer cells and the ageing cells, the scientists found that it was the ECM, which was ‘bringing the cancer cells there and allowing them to better attach near the aged cells and spread faster’.
The team also conducted experiments on human cells to find out if the predictions of the computer simulations replicated themselves.
They found that the cancer cells stuck strongly to the ECM around the aged cells, and eventually cleared the aged cells away.
Further, the team also found the ECM formed by the ageing cells to have higher levels of protein such as fibronectin, laminin and hyaluronan compared to the ECM formed by the young cells. These proteins allowed the cancer cells to bind to the aged cell-ECM more strongly, they said.
The researchers also hoped that future research could help make drugs that killed senescent cells, as a combination therapy with chemotherapeutics to tackle cancer progression.
