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Cell-to-Cell signaling plays crucial role in early pancreatic cancer progression, study in mice reveals

Scientists from IRB Barcelona, located at the Barcelona Science Park, and Memorial Sloan Kettering Cancer Center in New York, have published in Science a high-resolution epigenetic map of how cells with a mutation in the KRAS gene acquire plasticity and drive cancer progression when exposed to inflammation. The study, conducted in mice, paves the way for new therapeutic approaches.

Genetic mutations are frequent and known causes of cancer, but they cannot explain the entire development of the disease. The new study published in Science shows that interactions between these mutations and external factors, such as tissue damage, can modify the identity and local environment of cells, promoting the emergence and progression of tumors.

In pancreatic cancer, these changes begin to occur between 24 and 48 hours after tissue damage; as a result, some cells with the oncogene KRAS mutation acquire the ability to send and receive many more signals than a normal cell, engaging in these “conversations” in a structured manner.

“This work has been made possible thanks to a synergy between experimental and computational science,” highlights Dr. Alonso-Curbelo from IRB Barcelona, who co-led the study along with researchers from Memorial Sloan Kettering Cancer Center in New York.

In this regard, the researchers’ computational predictions have been validated with various experimental techniques, such as imaging techniques that have shown the proximity of cell populations communicating with each other within the tissue. The researchers have been able to demonstrate that these conversations drive cancer development.

Understanding how these communication networks between cells function provides a new roadmap for the development of potential therapies that can block or slow down the progression of pancreatic tumors.

The study concludes a line of research initiated by Dr. Alonso-Curbelo to elucidate the mechanism by which inflammation promotes cancer initiation.

» Reference article: Cassandra Burdziak, Direna Alonso-Curbelo, Thomas Walle, José Reyes, Francisco M. Barriga, et al. “Epigenetic plasticity cooperates with cell-cell interactions to direct pancreatic tumorigenesis”. Science (2022) DOI: 10.1126/science.add5327

» Enllaç a la notícia: web de l’IRB Barcelona [+]