Pancreatic cancer is one of the most aggressive cancer types. A new study from Karolinska Institutet, in collaboration with the Department of Pathology at Karolinska University Hospital, shows that tumour cells grow not only in the connective tissue-rich environment typical of the disease, but also in damaged parts of the pancreas where normal tissue is altered. The findings may provide new insights into tumour development and treatment.
Pancreatic cancer is an aggressive disease, and unlike many other cancers, survival rates have barely improved. Researchers at Karolinska Institutet have now shown that pancreatic tumor cells not only spread in the connective tissue-rich environment that is a well-known characteristic of pancreatic cancer but also grow into damaged parts of normal pancreatic tissue. There, the cancer can create its own environment.
The study, published in Nature Communications, is based on samples from 108 patients who underwent surgery at Karolinska University Hospital. In almost all cancers, tumour cells were found in the tissue that produces digestive enzymes, but is damaged when tumour cells grow into it.
"We see that the tumour cells adapt to the environment they find themselves in. In damaged areas of normal pancreatic tissue, they exhibit different characteristics than in the connective tissue-rich part of the tumour," says Marco Gerling , a researcher at the Department of Clinical Science, Intervention and Technology , Karolinska Institutet, who led the study together with pathologist Carlos Fernández Moro .
May affect treatment response
The researchers also observed that tumour cells in the damaged areas more often had a so-called "classical" tumour profile, while cells in the connective tissue-rich part had a more aggressive profile. The damaged areas contained support cells that express a specific protein, NGFR, which has previously been linked to the healing process of damaged tissue.
"This type of damaged tissue may play a role in how the tumour develops and responds to treatment," concludes Marco Gerling.
The study was done in collaboration with doctors at Karolinska University Hospital and researchers at Uppsala University, SciLifeLab, and the University of Bergen. It has been funded by the Swedish Research Council, the Swedish Cancer Society, the Swedish Society for Medical Research, and Region Stockholm, among others. The researchers declare no conflicts of interest.
Publication
"An injury-associated lobular microniche is associated with the classical tumor cell phenotype in pancreatic cancer", Sara Söderqvist, Annika Viljamaa, Natalie Geyer, Anna-Lena Keller, Kseniya Ruksha, Carina Strell, Neda Hekmati, Alexandra Niculae, Jennie Engstrand, Ernesto Sparrelid, Caroline Salmén, Tânia D. F. Costa, Miao Zhao, Staffan Strömblad, Argyro Zacharouli, Poya Ghorbani, Sara Harrizi, Yousra Hamidi, Olga Khorosjutina, Stefina Milanova, Bernhard Schmierer, Béla Bozóky, Carlos Fernández Moro, Marco Gerling, Nature Communications, online, 26 September 2025, doi: 10.1038/s41467-025-63864-7
