Cancer cells turn to cannibalism to survive
A breast tumour formed in mice and treated with chemotherapy drug doxorubicin shows that some cancer cells (red nuclei) have been engulfed by other cancer cells (green cell membrane). [Tulane University School of Medicine]
Researchers from Tulane University School of Medicine, US, have discovered that some cancer cells survive chemotherapy by 'eating' neighbouring tumour cells.
Studies suggest that this act of 'cannibalism' provides these cancer cells with the energy needed to survive and initiate tumour relapse after a course of treatment is completed.
Chemotherapy drugs such as doxorubicin kill cancer cells by damaging the DNA, but cells that survive initial treatment can soon give rise to relapsed tumours.
This is a problem in breast cancers that retain a normal copy of a gene called TP53.
Instead of dying in response to chemotherapy-induced DNA damage, these cancer cells generally just stop proliferating and enter a dormant but metabolically active state known as senescence.
In addition to surviving chemotherapy, these senescent cancer cells produce large amounts of inflammatory molecules and other factors that can promote the tumour's regrowth.
Chemotherapy-treated breast cancer patients with normal TP53 genes are therefore prone to relapse and have poor survival rates.
"Understanding the properties of these senescent cancer cells that allow survival after chemotherapy treatment is extremely important," says Dr Crystal Tonnessen-Murray, from James G. Jackson's laboratory at the School of Medicine.
A senescent cancer cell engulfs a neighbouring cell [Tulane University School of Medicine]
In the new study, Tonnessen-Murray and colleagues discovered that, after exposure to doxorubicin or other chemotherapy drugs, breast cancer cells that become senescent frequently engulf neighbouring cancer cells.
The researchers observed this surprising behaviour not only in cancer cells grown in the lab, but also in tumours growing in mice.
Lung and bone cancer cells are also capable of engulfing neighbours after becoming senescent, the researchers discovered.
Tonnessen-Murray and colleagues found that senescent cancer cells activate a group of genes that are normally active in white blood cells that engulf invading microbes or cellular debris.
After engulfing neighbours, senescent cancer cells digested these cells by delivering them to lysosomes, acidic cellular structures that are also highly active in senescent cells.
Importantly, the researchers determined that this process helps senescent cancer cells stay alive.
"Inhibiting this process may provide new therapeutic opportunities, because we know that it is the breast cancer patients with tumours that undergo TP53-mediated senescence in response to chemotherapy that have poor response and poor survival rates," says Jackson.
Research is published in Journal of Cell Biology.