The growth of pancreatic cancer cells (blue) is often aggressive.Credit: USC Norris Comprehensive Cancer Center/National Cancer Institute/SPL
Decoding aggression
Pancreatic cancer is extremely aggressive. One reason for this is the dense physical barrier that surrounds the tumour, known as the stroma. This is composed of tumour cells, and a network of proteins and other cell types, such as fibroblasts. The stroma protects cancer cells from the body’s immune response and from drugs intended to treat the malignancy.
Nature Outlook: Pancreatic cancer
Stroma fibroblasts were known to secrete galectin-1 (Gal-1), a sugar-binding protein that helps cancer cells to grow. But an international team led by Pilar Navarro at the Institute of Biomedical Research of Barcelona, Spain, has now identified Gal-1 inside the nuclei of fibroblasts, in which it regulates the expression of several cancer-associated genes, including KRAS. Because Gal-1 fuels the production of KRAS protein inside fibroblasts, these cells stay activated, promoting tumour growth and spread.
The newly-discovered location of Gal-1 expands the focus of therapies that inhibit it. Researchers say that targeting Gal-1, both in and outside cells, is a promising strategy that might help to improve outcomes for people with pancreatic cancer. Therapies that can enter tumour-associated fibroblasts and block Gal-1 in the nucleus might help to reprogram the cells into a less aggressive and activated state, potentially diminishing their role in tumour development and aggression.
Proc. Natl Acad. Sci. USA 122, e2424051122 (2025)
Encrypted proteins
The ‘dark genome’ — the 98% of a person’s genetic code that is not usually used to produce proteins — is now known to be used by some cells to produce short chains of amino acids known as cryptic peptides. Now, a team of researchers has identified hundreds of cryptic peptides that are specific to pancreatic tumours.
A team led by William Freed-Pastor at the Dana-Farber Cancer Institute in Boston, Massachusetts, and Tyler Jacks at the Koch Institute at Massachusetts Institute of Technology, Cambridge, used human tumour samples to produce pancreatic organoids — simplified 3D versions of the larger cancerous organ — and extracted the peptides from the surface of the cells. The team then attempted to find matches for these peptides in healthy tissues. It found roughly 500 cryptic peptides that are not produced by normal cells, and seem to be unique to pancreatic cancer.
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