Cannibalism among survivors

After chemotherapy, cancer cells can devour competitors

Polina Gershberg, Naked Science

Scientists from the Tulane University of Louisiana Medical School have studied the mechanisms of tumor recurrence after chemotherapy. The results of the work are published in the Journal of Cell Biology (Tonnessen-Murray et al., Chemotherapy-induced senescent cancer cells engulf other cells to enhance their survival).

The repeated development of cancerous tumors after treatment and subsequent remission is due to the presence of so-called LCC cells (latent cancer cells), which are also sometimes called dormant tumor cells. This is a kind of "reserve cancer regiment": due to the slow metabolism and lack of division, they are insensitive to chemotherapy and are able to evade the immune response. After some time after treatment, LCC cells are able to go into an active state and cause a relapse.

The researchers wanted to learn more about how such dormant cells survive during treatment. To do this, they treated human breast cancer cells with doxorubicin, an antitumor drug. The treated cells were then mixed with similar untreated cancer cells.

Doxorubicin destroys cellular DNA and suppresses the synthesis of nucleic acids. Cells that are in the phases of active DNA synthesis and post-synthetic activity (S- and G2-phases of the cell cycle, respectively) are sensitive to it. But some of these cells do not die under the influence of the drug, but go into "sleep mode" — they turn into LCC. Scientists have found that this is how cells with a healthy (non-mutant) TP53 gene behave, which encodes a tumor suppressor protein.

During the experiment with breast cancer cells, scientists saw that LCC cells formed under the influence of doxorubicin stopped dividing, but were not completely inactive. In these cells, lysosomes (organelles that play the role of a "cellular stomach") increased and genes that are usually used by leukocytes to absorb pathogenic microorganisms were activated.

Moreover, in a mixture of treated and untreated LCC cells, intact tumor cells that were not treated with doxorubicin were often absorbed and digested. This gives the dormant cells the supply of substances and energy needed during the subsequent transition to the active state. Scientists even managed to capture the absorption process on video. 

The process of absorption by an LCC cell of an untreated active cancer cell / ©Tulane University

At the same time, the reverse process was not observed: untreated cells never sought to absorb LCC. According to the researchers, inhibiting the "cannibalism" of cancer cells can improve the prognosis of survival among patients who have cancer cells with the non-mutant T53 gene.

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