A research group led by Associate Professor Toshiro Sato of Keio University succeeded in efficiently multiplying 39 human-derived pancreatic cancer cells in vitro, and detailed analysis revealed that pancreatic cancer is associated with the surrounding environment. It was clarified that it becomes malignant by being able to proliferate without depending on the cell proliferation substance given from.
The survival rate of pancreatic cancer is the lowest of all cancer types.It is thought that this is because pancreatic cancer progresses asymptomatically and is often found in difficult surgical conditions, and the effect of anticancer drug treatment does not last long.In recent years, analysis of genetic information on pancreatic cancer has revealed that there is a difference in the survival time of pancreatic cancer patients, but the cause has not been clarified and it has not been applied to treatment.
The research group found that two substances, Wnt and Rspondin, which work from the outside of the cells and stimulate the growth of normal pancreatic cells, are deeply involved in the malignant transformation of pancreatic cancer.In addition, pancreatic cancer has three types that gradually become malignant depending on whether these two substances are required for the growth of pancreatic cancer itself ((2) Wnt non-secretory type, (2) Wnt secretory type, and (3) Wnt / R spondin-independent type. ) It turned out that it can be classified.Furthermore, it was clarified that the difference in the type is linked to the amount of expression of the gene GATA6.
In addition, the research group created artificial pancreatic cancer using a gene modification technology called the CRISPR / Cas9 system, and succeeded in reproducing the process of pancreatic cancer becoming malignant.
This research is the first in the world to clarify the mechanism of gradual malignant transformation using technology to efficiently proliferate human-derived pancreatic cancer cells.In the future, elucidating the mechanism of the gene expression program for pancreatic cancer by GATA6 is expected to be a breakthrough in formulating new therapeutic strategies for pancreatic cancer.
Paper information:[Cell Stem Cell] Human Pancreatic Tumor Organoids Reveal Loss of Stem Cell Niche Factor Dependence during Disease Progression
