‘Pac-Man’ protein tells cells to eat sickly neighbors

Scientists have identified a protein that gives cells the signal to eat dying neighbors. The action helps prevent inflammation.

Researchers made the discovery about the Pac-Man–like protein, called Rac1, while studying lactation and how the female breast gets rid of dead cells and surplus milk when they’re no longer required.

In pregnancy, specialized epithelial cells in the breast grow to form alveoli that secrete milk. When the milk supply is no longer required, the alveoli die and the breast reverts back to a non-pregnancy state. Breast epithelia also line the mammary ducts, which transport milk towards the nipple when required.

Through gene deletion studies, researchers found the Rac1 protein is crucial both for the secretion of milk and its removal in the drying-up period that follows.

Links to cancer

More than 90 percent of cancers come from epithelial cells, which is why unlocking the mystery of how they work is essential.

“Rac1 is over expressed in various cancers including breast cancer, and Rac1 inhibitors are currently being considered as anticancer therapies,” says Nasreen Akhtar of the oncology and metabolism department at the University of Sheffield. “However, until now virtually nothing was understood about what Rac1 does in healthy tissue … our study shows that in the breast one of its central roles is to prevent harmful inflammatory responses. Without Rac1 these responses are heightened and prolonged within tissues.

“Given that sustained inflammation is linked to cancer progression, the findings show that blocking Rac1 might not be a good idea.”

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Inflammatory phagocytes from the immune system are normally recruited to clear up dead cells lurking in tissues and surplus fluids. If too many are recruited for extended periods, they can trigger inflammation within tissues, causing damage.

The new study shows that the breast epithelia use Rac1 to evade harmful inflammatory phagocytes from the immune system by hijacking their job.

In the first few days after weaning, live breast epithelia eat their dying neighbors and swallow all of the secretions, clearing the ducts from old milk and dead cells. The phagocyte-like breast epithelia then die themselves and these are subsequently cleared up by professional phagocytes from the immune system.

“By doing the job themselves, the breast epithelia limit both the numbers and time of immune phagocyte infiltration, which protects the tissue from becoming damaged,” says Akhtar.

“Without Rac1, the dead cells and milk flood the interconnecting breast ducts causing them to bloat and triggering chronic inflammation. The bloated ducts then fail to regenerate and produce milk in a future pregnancy.”

The findings appear in the journal Developmental Cell.

“It is thought that we shed the equivalent of our own body weight in dead cells every year,” Ahktar says. “However, very little is known about how we get rid of them. If immune phagocytes were the only cell type to clear up cell corpses our bodies would be continuously inflamed. It’s quite likely that epithelial engulfment occurs in many other organs because this cell type forms the building blocks of our bodies.”

Source: University of Sheffield