Annual Report 2021
Cancer Cell Systems Unit
Keisuke Sekine, Tatsuya Kometani, Kaoru Miyazawa, Ta-Chun Lin, Takumi Yamada, Koya Ichikawa, Hikaru Kondo
Introduction
Pancreatic cancer is an intractable cancer with a poor prognosis and is expected to account for the second largest number of cancer deaths by 2030. The development of effective treatments is therefore an urgent issue. The survival, maintenance, and changes of cells in a cell society are always influenced by the surrounding cells. Pancreatic cancer is particularly abundant in stromal cells, and it is thought that the cancer cell society formed by the stromal cells together with the pancreatic cancer cells is deeply involved in malignancy and treatment resistance. There are, however, many unknowns regarding the pancreatic cancer cell-stroma interactions. The processes by which the interactions between mutated epithelial cells and surrounding stromal cells change to promote and suppress tumorigenesis by epithelial cells and to develop treatment resistance remain unclear. Therefore, elucidation of the cancer ecosystem created by the pancreatic epithelial cell-stroma interactions-that is, the evolution of the epithelial cell-stroma interactions in the processes that disrupt normal pancreatic epithelial tissue to form a cancer cell society-starts with its formation. It is important to understand the processes leading to the acquisition of drug resistance and the ability to metastasize, and to control them. The goal of this unit is to elucidate the interactions between pancreatic epithelial cells and the interstitium, which are thought to be 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 are establishing patient-derived primary pancreatic cancer organoids and artificial cancer tissues, including stroma. We are also working to elucidate the pancreatic epithelial cell-stroma interactions through organoid analysis at the single-cell level and spatial transcriptomics that retain spatial information.
Research activities
A system for obtaining pancreatic cancer surgical specimens was established, and primary pancreatic cancer organoids were established from them. Pancreatic cancer organoids have also been established from PDXs. The establishment efficiency is considerably high even if we only count the ones that can be stocked after culturing. In addition, we are trying to elucidate cancer metastasis in vivo and also in vitro using artificial cancer tissue.
Education
We accepted one graduate student and four undergraduate students as trainees.
Future Prospects
The establishment of primary pancreatic cancer organoids is progressing smoothly, and we expect to be able to form an organoid library by continuing to establish them. We are also trying to elucidate cancer cell-stroma interactions by transcriptome analysis, and identify therapeutic target molecules by functional analysis.