Study Finds that Pancreatic Cancer Thrives on Mucus

By understanding the precise composition of a tumor, we can enhance our capacity to combat cancer. However, gaining that knowledge is not simple. Clusters of cancer cells that are always changing make up tumors. Some turn into prevalent cancer variations. Some develop into more lethal, resistant forms of medication. Nobody really knows what causes this erratic conduct. Professor David Tuveson of Cold Spring Harbor Laboratory (CSHL) and his colleagues have now discovered mucus, a process implicated in the metamorphosis of pancreatic cancer.

Mucus is produced by pancreatic cancer cells in the early stages of the disease. These cells also rely on the body’s mechanisms that control the formation of mucus. This new information may contribute to the development of future treatments or diagnostic approaches.

The dynamic and erratic nature of tumors makes it difficult to determine which treatments are best for individuals. Leading the study was Claudia Tonelli, a research investigator in the Tuveson lab. “We need to understand this concept of cell plasticity better and design therapy that takes this into consideration,” she says.

Tonelli collaborated with Jonathan Preall of CSHL’s Single-Cell Biology Facility to investigate the cause of the unpredictable behavior of malignancies. Collectively, the researchers dissected haphazard clusters of pancreatic tumors into separate cancer cells. They might then investigate the particular variations among every kind of pancreatic cancer. And that’s when the significance of mucus in the differentiation of cancer became clear.

It is difficult and messy for cancer cells to produce mucus. These protein blobs require a lot of resources to form and export. So why even bother doing anything at all? The researchers found that mucus is essential for the survival and growth of low-grade pancreatic cancer cells of the classical type, a common kind.

The cancer cells appear to grow out of this dependence as they develop into a more lethal basal-like form. Tonelli believes that mucus might shield nascent cancer cells from the immune system.

It’s a double-edged sword, but medically targeting mucus in immature, susceptible pancreatic cancer cells may have some benefits. Cancer cells stop proliferating when the creation of mucus is inhibited. However, as a survival strategy, this drives some of them to transform into more deadly basal-like cancer cells.

“We would have to do further studies to be ready to hit the cancers once they have undergone this differentiation,” Tonelli said. “Identifying a combination of therapies may be an option.”

One day, researchers may be able to find more effective treatments by understanding what causes pancreatic cancer cells to change. Therefore, even if mucus may not hold the secret to curing pancreatic cancer, it may be possible to discover the solution right in front of us.

More information: Claudia Tonelli et al, A mucus production programme promotes classical pancreatic ductal adenocarcinoma, Gut (2024). DOI: 10.1136/gutjnl-2023-329839

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