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Inflammation serves to kill invading bacteria and viruses. Certain molecules on the surface of the microbes can trigger an inflammatory cascade, and one example of such a molecule is lipopolysaccharide (LPS). Cells can react to LPS by triggering a process called pyroptosis that causes the cell to burst and die. The released cell contents attract blood and lymphatic cells that in turn kill the LPS-producing bacteria. This prevents the bacteria from multiplying and spreading.
LPS was used in the very early days of medicine to treat cancer, although it has fallen out of favor because it causes severe side effects, such as a hyperinflammatory response (sepsis) that can result in death. It was not known exactly how LPS kills cancer cells, which has limited its use. Yokoyama et al. now show that a protein called SCGB3A2, which is produced by the cells that line the lung airways, binds to LPS. Tests on mouse immune cells and lung cancer cells grown in the laboratory showed that the resulting SCGB3A2-LPS complex can then bind to a cell surface protein called syndecan 1. This enables LPS to enter the cell and trigger pyroptosis and cell death.
To confirm the role of SCGB3A2 in pyroptosis, Yokoyama et al. examined tumor growth in mice that are not able to produce SCGB3A2. These mice developed more tumors than normal mice, but tumor growth was suppressed when mice were injected with SCGB3A2.
The findings presented by Yokoyama et al. could potentially lead to new types of cancer treatments, particularly for lung cancers. However, it remains to be examined whether molecules that trigger pyroptosis, like LPS, could also be used to treat cancers other than those from the lung. Further work is also needed to understand in more detail how SCGB3A2 and LPS work together to cause cancer cell death.
