According to the findings published in a journal called ‘eLife’, cancer cells get more aggressive and evade cell death when they squeeze through tight spaces
Cancer studies and what factors govern its metastasis or spread had been concerning cancer research since the disease was discovered. Now, a new study finds that mechanical stress causes cancer cells to mutate and increase uncontrollably. According to the findings published in a journal called ‘eLife’, cancer cells get more aggressive and evade cell death when they squeeze through tight spaces. This makes cells spread more unsparingly.
Metastasis is considered to be the cause of most deaths from concern. With this new finding, scientists will try to find out a solution to spread cancerous cells with a new approach. With a tight squeeze, cancer cells can escape their tumour, enter capillaries and spread through the body. In this process, the cancerous cells change their shape and evade the immune system, making them stronger. This process is called confined migration.
First author of the study, Deborah Fanfone, Postdoctoral Fellow at the Cancer Research Centre of Lyon, France explains that mechanical stress causes cancer cells to mutate and increase in cell number with greater tissue invasion. The study intends to find out if mechanical stress increases the chances of cells to metastasis and how it happens.
For the purpose of the study, the researchers forced human breast cancer cells through a membrane with tiny, three-micrometer sized holes to stimulate an environment of confined migration. Fanfone and his colleagues found that after going through the membrane just once, the cells became more mobile and resistant to anoikis, a programmed cell death that occurs when cells become detached from the surrounding network of proteins and other molecules that support them. The cells escaped destruction by immune natural killer cells.
Moreover, increased expression of inhibitory-of-apoptosis proteins (IAPs) increased the resistance of the cancer cells to cell death. On treating the cancer cells to a SMAC mimetic, a cancer drug, expression of inhibitory-of-apoptosis proteins decreased, removing the protection.
The team then subjected immune-suppressed mice with breast cancer cells that had undergone confined migration and found that the mice developed more lung metastases than mice that were administered with breast cancer cells that had not been exposed to confined migration.
Senior author Gabreil Ichim who leads the Cancer Cell Death team at cancer research Centre of Lyon says the study showed how mechanical stress or confined migration boosts survival in cancer cells and makes them more prone to metastasis.
The author concluded that these results will lead to additional studies on how to treat metastases effectively by controlling mechanical stress cells undergo, such as therapy that soften tumours etc. The study also found SMAC mimetics currently undergoing clinical trials as a possible new treatment approach.