Annual Report 2023
Laboratory of Cancer Cell Systems
Keisuke Sekine, Ta-Chun Lin, Miyabi Tominaga, Hinako Sumiyoshi
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 laboratory 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. Furthermore, we are working on establishing patient-derived cells from various valuable cancer specimens using cancer organoid technology.
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. We are advancing the establishment of organoids from normal tissue and other cancer types to analyze the process of the accumulation of genetic mutations and drug development.
Research Activities
A system for obtaining pancreatic cancer surgical specimens was established. Primary pancreatic cancer organoids were established from them and their use in drug efficacy evaluations is underway. 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. For metastasis analysis, we are trying to elucidate cancer metastasis in vivo and also in vitro using artificial cancer tissue. We have also begun development of artificial tissue creation technology for analyzing cancer metastases and started analyzing in vivo analysis methods. Since organoids are effective in various analyses, we are actively advancing the establishment of organoids from other cancer types and normal tissues and utilizing them for preclinical drug efficacy evaluations.
Education
We accepted one graduate student and one undergraduate student 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.
List of papers published in 2023
Journal
1. Kometani T, Kamo K, Kido T, Hiraoka N, Chibazakura T, Unno K, Sekine K. Development of a novel co-culture system using human pancreatic cancer cells and human iPSC-derived stellate cells to mimic the characteristics of pancreatic ductal adenocarcinoma in vitro Biochem. Biophys. Res. Commun. 658: 1-9 (2023) doi: 10.1016/j.bbrc.2023.03.061