Department of Cell Culture Technology / Department of Patient-Derived Cell Line and Xenograft

Tohru Kiyono, Farhana Ishrat Ghani, Chiho Kohno

Introduction

There are mainly two approaches to amplify cancer cells from patients, in vitro cell culture and patient-derived xenograft (PDX). Since HeLa cell line, the first human cancer cell line, has been established, human cancer cell lines have been essential for cancer research. Patient-derived xenografts (PDXs) generated from fresh tumor specimens generally reflect histopathology, tumor behavior, and the metastatic properties of the original tumor. Both PDX models and cell line-derived xenograft (CDX) models are considered to be important preclinical tools in recent years. However, the success rate to establish new cell lines or PDX lines is not satisfactory.

Our team and what we do

The Department of Cell Culture Technology and the Department of Patient-Derived Cell Line and Xenograft were founded in 2014 for developing better methods to amplify normal human cells as well as cancer cells derived from clinical specimens obtained by operation, biopsy, and therapy. With the help of the Pathology Division, we have started to store valuable cancer specimens systematically so that cancer tissues or cancer cells can be transplanted into immune-deficient mice or cultivated in vitro in the future.

Research activities

Based on the improved method developed by the Division of Carcinogenesis and Prevention, we now can cultivate so far difficult-to-cultivate primary human cells, such as hepatocytes, pancreatic duct cells, gastric epithelial cells, and colon epithelial cells without feeder cells. A method for a long-term culture of these cell types has been established, and also can be immortalized by transduction of CDK4, cyclin D1, and TERT so as to be cultivated in more general culture conditions.

So far we have banked more than 50 live ovarian cancer specimens in a deep freezer. Among them, we have established 19 ovarian cancer cell lines. Cell line-derived xenografts (CDX) were confirmed to faithfully recapitulate the features of original tumors. We are searching for methods to establish cancer cell lines from a given cancer other than ovarian cancer.

Future prospects

Cancer cell lines established by ordinary culture methods generally do not maintain the features of original tumors. Additional mutations in p15/p16 genes and pathological features of xenograft tumors are often different from original tumors. We have established a new culture method to amplify ovarian cancer cells with almost 100% efficiency. Xenograft tumors faithfully recapitulated the features of original tumors. Since we have developed a method to efficiently establish ovarian cancer cell lines, we will expand our method to other cancers. These cell lines are valuable resources with detailed clinical information. Systematic storage of live materials from valuable clinical samples is now under development.

Established cell lines with clinical information and genomic data could be used for many researches including validation of drug sensitivity estimated from clinical sequencing. Rapid and efficient establishment of cell lines will provide drug sensitivity of the cell lines to the doctor before drug administration to patients in the future.