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Establishment and characterization of a new malignant peritoneal mesothelioma cell line, KOG-1, from the ascitic fluid of a patient with pemetrexed chemotherapy resistance

Abstract

Malignant peritoneal mesothelioma (MPeM) is a rare and aggressive form of malignant mesothelioma. Sufficient biological tools for studying the functional characteristics of this cancer have not been developed. Therefore, in this study, a novel human cancer cell line, KOG-1, was established from ascites fluids isolated from a 39-year-old Japanese woman with pemetrexed-resistant MPeM. Cells were dendritic or linear immediately after thawing, showed a jigsaw puzzle-like and spindle arrangement during growth, and formed monolayers without contact inhibition in two-dimensional (2D) culture. The population doubling time was 13.7 h. Karyotypic and molecular genetic analyses showed that chromosome numbers ranged from 62 to 142, with a peak of 73 with complicated copy number alterations. No germline BAP1 pathogenic variant was detected. Cells expressed various tumor markers of mesothelioma, such as calretinin, podoplanin, and Wilms tumor 1 (WT-1). Drug sensitivity and resistance testing with a set of 36 drugs using 2D and three-dimensional (3D) culture models demonstrated that KOG-1 cells showed high and low sensitivity to pemetrexed under 2D and 3D culture conditions, respectively, whereas control ovarian cancer cell lines showed low sensitivity to pemetrexed under both culture conditions. This newly established cell line will be a valuable biological resource to expand the feasibility of functional studies as well as drug testing for potential therapeutic purposes in MPeM.

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Acknowledgements

We thank the patient and the supporting medical staff for making this study possible. We are also grateful to Ms. Tomomi Noda, Ms. Atsuko Fukushima, and Ms. Shihomi Yamaguchi for administrative assistance and biobank data management, and Mr. Ippei Sakamoto and Mr. Shigeki Tanishima for NGS data management.

Funding

This work was supported by the JSPS Bilateral program and the KAKENHI (Grant Nos. 18K09298, 19K09833).

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Correspondence to Tomoko Akahane.

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Supplemental Fig. 1. List of genes containing the target sequences (PPTX 53 kb)

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Akahane, T., Hirasawa, A., Imoto, I. et al. Establishment and characterization of a new malignant peritoneal mesothelioma cell line, KOG-1, from the ascitic fluid of a patient with pemetrexed chemotherapy resistance. Human Cell 33, 272–282 (2020) doi:10.1007/s13577-019-00286-w

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Keywords

  • Peritoneal mesothelioma
  • Cell line
  • Drug sensitivity and resistance testing
  • Two- and three-dimensional culture
  • Pemetrexed