Annual Report 2020
Laboratory of Cancer Cell Systems
Keisuke Sekine, Kaoru Miyazawa
Introduction
Pancreatic cancer is an intractable cancer with a poor prognosis and is expected to be the second largest number of cancer deaths in 2030, and the development of effective treatments is an urgent issue. The survival, maintenance, and change of cells in a cell society are always influenced by surrounding cells. Pancreatic cancer is particularly abundant in stromal cancer, and it is thought that the cancer cell society formed by the stromal cells together with pancreatic cancer cells is deeply involved in malignancy and treatment resistance. There are, however, many unknown aspects regarding pancreatic cancer cell-stromal interaction. The process of how the interaction between mutated epithelial cells and surrounding stromal cells changes to promote and suppress tumorigenesis by epithelial cells and to develop treatment resistance remains unclear. Therefore, the elucidation of the cancer ecosystem created by the pancreatic epithelial cell-stromal interaction, that is, the evolution of the epithelial cell-stromal interaction in the process of disruption of normal pancreatic epithelial tissue to form a cancer cell society, progresses from its formation. It is important to understand the process leading to the acquisition of drug resistance and the ability to metastasize, and to control it. The goal of this unit is to elucidate the interaction between pancreatic epithelial cells and the interstitium, which is considered essential for the development and progression of pancreatic cancer.
The Team and What We Do
We aim to elucidate and control the cancer ecosystem. We establish patient-derived primary pancreatic cancer organoids and artificial cancer tissues including stroma. We also elucidate pancreatic epithelial cell-stromal interaction through organoid analysis at the single cell level and spatial transcriptomics that retains spatial information.
Research activities
A system for obtaining pancreatic cancer surgical specimens was established, and primary pancreatic cancer organoids were established from pancreatic cancer surgical specimens. Pancreatic cancer organoids have also been established from PDX. The establishment efficiency is considerably high even if we count only the one that can be stocked after culturing. In addition, we are trying to establish genome editing technology for carrying out genetic modification of oncogenes, constructed a simple analysis system for improving editing efficiency, and worked on improving the genome editing technology using cancer organoids.
Education
We accepted one graduate student as a trainee.
Future Prospects
The establishment of primary pancreatic cancer organoids is progressing smoothly, and we expect that the organoid library can be established by continuing the establishment in the future. Moreover, as genome editing technology and organoid technology have a high affinity, it is important to continue to improve them. Transcriptome analysis is important for heterogeneity analysis of pancreatic cancer, and will advance the elucidation of pancreatic epithelial cell-stromal interactions.
List of papers published in 2020
Journal
1. Takada K, Aizawa Y, Sano D, Okuda R, Sekine K, Ueno Y, Shoji Nakayama S, Jun Aoyama J, Sato K, Kuwahara T, Hatano T, Takahashi H, Arai Y, Nishimura G, Taniguchi H, Oridate N. Establishment of PDX-derived salivary adenoid cystic carcinoma cell lines using organoid culture method. Int J Cancer . 148(1):193-202. (2021) doi: 10.1002/ijc.33315. Epub 2020 Oct 7.
2. Sekine K, Ogawa S, Tsuzuki S, Kobayashi T, Ikeda K, Nakanishi N, Takeuchi K, Kanai E, Otake Y, Okamoto S, Kobayashi T, Takebe T, Taniguchi H
Generation of human induced pluripotent stem cell-derived liver buds with chemically defined and animal origin-free media. Scientific Reports 10(1):17937. (2020) doi: 10.1038/s41598-020-73908-1.
3. Sekine K, Tsuzuki S, Yasui R, Kobayashi T, Ikeda K, Hamada Y, Kanai E, Camp JG, Treutlein B, Ueno Y, Okamoto S, Taniguchi H
Robust detection of undifferentiated iPSC among differentiated cells. Scientific Reports 10(1):10293. (2020) doi: 10.1038/s41598-020-66845-6.