A cross-section of a mouse’s early-stage pancreatic tumor. CSHL scientists discovered that early pancreatic cancer cells depend on the regulators of mucus production to survive and grow. Green, purple, yellow, cyan, and white denote areas where mucus production is high. Credit: Tuveson lab/Cold Spring Harbor Laboratory
Key points:
- At the early stage, low-grade pancreatic cancer cells produce mucus that helps them survive and protects them against the immune system.
- Researchers broke down pancreatic tumors into individual cancer cell types and found that the late-stage basal-like pancreatic cancer cells no longer depended on mucus.
- Future studies can target pancreatic cancer cells that have undergone maturation to identify better diagnostic and therapeutic strategies.
Identifying the composition of a tumor would make it easy to treat cancer. However, tumors are clusters of constantly changing cells that can become common variants or deadly, drug-resistant varieties.
Now, new research, published in Gut, uncovers a mucus-based mechanism involved in pancreatic cancer cell transformation. This discovery may be able to change the landscape of future diagnostic or therapeutic strategies.
At the early stage, pancreatic cancer cells produce mucus. By breaking down messy clumps of pancreatic tumors into individual cancer cells, the researchers could examine mucus’s role and the differences between each pancreatic cancer cell type.
The researchers found that low-grade pancreatic cancer—called the classical type—depended on mucus to survive and thrive as it protects them against the immune system. When cancer cells matured and transformed into a deadlier type—called basal-like—they no longer depended on mucus.
While it appears promising to target young, vulnerable pancreatic cancer cells, this treatment strategy has its drawbacks. The team found that cancer cells stop growing when mucus production is blocked, but this triggers a survival mechanism that forces some cells to transform into deadlier basal-like cancer cells.
“We would have to do further studies to be ready to hit the cancers once they have undergone this differentiation,” said study lead Claudia Tonelli of Cold Spring Harbor Laboratory. “Identifying a combination of therapies may be an option.”
In the future, the team hopes their findings about pancreatic cancer cell transformation can inform better therapeutics.