Macropinocytosis: Cancer Cells Consume Themselves to Endure Life-Threatening Damage


It is the membrane of cancer cells that is at the center of the new study now presenting an entirely new approach in which cancer cells can repair the damage that can otherwise eliminate them.

The cell membrane in both cancer cells and normal cells acts as the skin of the cells. And damage to the membrane can be life-threatening. Fluid is present inside the cells, and if the cell rapture, the cell simply floats out and dies — a bit like a hole in a water balloon.

Hence, injury to the cell membrane must be repaired immediately, and a new study from a group of Danish scientists reveals that cancer cells use a technique called macropinocytosis. The technique, which is previously a recognized tool for cells in other circumstances, consists of the cancer cells extracting the intact cell membrane over the infected area and sealing the hole in a matter of minutes. Next, the infected part of the cell membrane is distributed into small spheres and transported to the cells’ “stomach” — the so-called lysosomes, where they are broken down.

Macropinocytosis

The method is utilized by cells to absorb, for example, molecules or water outside the cell. Immune cells also used this method when they enclose and consume foreign bodies such as viruses or bacteria — a technique that is essential for the immune system’s ability to resist infections.

In the laboratory, the scientists damaged the cancer cells membrane using a laser that executes tiny holes in the membrane and triggers macropinocytosis. Here they can observe that if the method is restrained with substances obstructing the formation of the small membrane spheres, the cancer cell can no longer repair the damage and dies.

“Our study gives fundamental information about how cancer cells sustain. In our analyses, we have also pointed that cancer cells die if the process is inhibited, and this leads towards macropinocytosis as an aim for future treatment. It is a long-term prospect, but it is exciting,” says team leader Jesper Nylandsted from the University of Copenhagen and the Danish Cancer Society’s Research Center, who has supervised the new study and who for many years has examined how cancer cells repair their membranes.

Possibility of Recycling

One of the most critical attributes of cancer is when it starts to spread in the body. If tumors spread in new parts of the body, it becomes more challenging to treat and typically needs more extensive modes of treatment. It is also when tumor cells reached through the body’s tissues that they are likely to damage their membrane.

Scientists at the Danish Cancer Society have earlier explained how cancer cells can use another method to repair the membrane, particularly by tying off the infected part, rather like when a lizard throws its tail.

Though, the trials in the lab could indicate that particularly aggressive cancer cells use macropinocytosis. Since the cancer cell has the opportunity to reuse the damaged membrane when it is degraded in the lysosomes. This kind of recycling will be beneficial for cancer cells as they divide constantly, requiring large amounts of material and energy for the new cells.

And although the scientists have now announced the new results, their work is not over. This is described by another member of the study team, postdoc Stine Lauritzen Sønder:

“We remain to work and examine how cancer cells defend their membranes. In association with macropinocytosis, in particular, it is also exciting to see what happens after the membrane is closed. We understand that the first patching is a bit harsh and that a more thorough repair of the membrane is required afterward. It can be another weak point in the cancer cells, and is something we need to study,” she says.

Journal Reference:

“Restructuring of the plasma membrane upon damage by LC3-associated macropinocytosis” by Stine Lauritzen Sønder, Lisa B. Frankel, Catarina Dias, Adam Cohen Simonsen, Swantje Christin Häger, Anne Sofie Busk Heitmann, and Jesper Nylandsted, 2 July 2021, Science Advances.

DOI: 10.1126/sciadv.abg1969


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