Cancer Cells Exhibit Cannibalism to Survive Chemotherapy: Here’s How

There are several classes of chemotherapy drugs, based on their mechanism of action. Some examples include the following:

• Alkylating Agents: Cisplatin, Chlorambucil, Procarbazine, and Carmustine
• Antimetabolites: Methotrexate, Cytarabine, and Gemcitabine
• Antimicrotubule Agents: Vinblastine and Paclitaxel
• Topoisomerase Inhibitors: Etoposide and Doxorubicin
• Cytotoxic Agents: Bleomycin and Mitomycin

Chemotherapy drugs such as doxorubicin damage the DNA (deoxyribonucleic acid) of the cancer cells, thereby killing them. However, a small proportion of these cancer cells may survive the initial course of chemotherapy, which can give rise to relapsed tumors.

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Tumor relapse is especially a problem in case of breast cancer, which retains a normal copy of the TP53 gene that encodes the tumor protein p53 (p53). The p53 protein is a tumor suppressor, which is responsible for regulating cell division by preventing cells from dividing and proliferating too fast or in an uncontrolled fashion.

The cancer cells that survive the onslaught of chemo drugs are responsible for causing a relapse. These surviving cancer cells generally stop proliferating and enter a dormant yet metabolically active state of suspended animation known as senescence. Interestingly, these senescent cancer cells produce copious amounts of inflammatory molecules and other factors that promote tumor reactivation. Therefore, chemotherapy-treated breast cancer patients having a normal copy of the TP53 gene are prone to relapse and have a poor survival rate.

"Understanding the properties of these senescent cancer cells that allow their survival after chemotherapy treatment is extremely important," says Dr. Crystal A. Tonnessen-Murray, a Postdoctoral Fellow in Jackson's laboratory at the Tulane University School of Medicine, USA.

Uniqueness of the Study

The study is unique due to the fact that it has made a ground-breaking discovery about the behavior of cancer cells, which was not known before. The research team found that breast cancer cells that survive chemotherapy and enter into a phase of senescence, frequently engulf adjacent cancer cells - a phenomenon akin to cannibalism.

The research team was surprised to find that this cannibalistic behavior was not only exhibited by cancer cells grown in cell culture in the laboratory, but also in tumors growing in mice. The research team also discovered that lung and bone cancer cells that had undergone senescence were also capable of engulfing their neighboring cancer cells.

It was further revealed that the senescent cancer cells activated a group of genes that are also found in white blood cells (WBC), which are responsible for engulfing pathogenic microbes or dead cellular debris. Subsequently, these materials are degraded in cellular organelles known as lysosomes, which have an acidic environment, thereby facilitating digestion. Likewise, the senescent cancer cells, after 'eating' their neighboring cancer cells, also digest the cellular debris within their lysosomes.

Implications of the Study

The phenomenon of cannibalism that is exhibited by cancer cells helps them to stay alive. Senescent cancer cells that engulfed a neighboring cancer cell survived significantly longer in cell culture, compared to those that didn't exhibit this cannibalistic behavior.

Engulfing neighboring cancer cells could provide the senescent cancer cells with the necessary energy resources for them to survive the attack of chemo drugs, as well as produce factors responsible for bringing about tumor relapse.

Concluding Remarks

Jackson concludes: "Inhibiting this process may provide new therapeutic opportunities because we know that it is the breast cancer patients with tumors that undergo TP53-mediated senescence in response to chemotherapy that have a poor response and poor survival rates."

Funding Source

The study was funded by the US Department of Defense, Virginia, the National Institutes of Health (NIH), and the NIH/National Institute of General Medical Sciences, Bethesda, Maryland, USA.

Reference :

1. Chemotherapy-induced senescent cancer cells engulf other cells to enhance their survival - (http://jcb.rupress.org/content/early/2019/09/16/jcb.201904051)

Source: Medindia