Skip to main content

Advertisement

SpringerLink
Log in

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

  • Cell Line
  • Published:
Human Cell Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Husain AN, Colby T, Ordonez N, Krausz T, Attanoos R, Beasley MB, Borczuk AC, Butnor K, Cagle PT, Chirieac LR, et al. Guidelines for pathologic diagnosis of malignant mesothelioma: 2012 update of the consensus statement from the International Mesothelioma Interest Group. Arch Pathol Lab Med. 2013;137:647–67.

    Article  Google Scholar 

  2. Husain AN, Colby TV, Ordonez NG, Allen TC, Attanoos RL, Beasley MB, Butnor KJ, Chirieac LR, Churg AM, Dacic S, et al. Guidelines for pathologic diagnosis of malignant mesothelioma 2017 update of the consensus statement from the international mesothelioma interest group. Arch Pathol Lab Med. 2018;142:89–108.

    Article  CAS  Google Scholar 

  3. Rodriguez D, Cheung MC, Housri N, Koniaris LG. Malignant abdominal mesothelioma: defining the role of surgery. J Surg Oncol. 2009;99:51–7.

    Article  Google Scholar 

  4. Mensi C, Mendola M, Dallari B, Sokooti M, Tabibi R, Riboldi L, Consonni D. Differences between peritoneal and pleural mesothelioma in Lombardy, Italy. Cancer Epidemiol. 2017;51:68–73.

    Article  Google Scholar 

  5. Baratti D, Kusamura S, Deraco M. Diffuse malignant peritoneal mesothelioma: systematic review of clinical management and biological research. J Surg Oncol. 2011;103:822–31.

    Article  Google Scholar 

  6. Bianchi C, Brollo A, Ramani L, Bianchi T, Giarelli L. Asbestos exposure in malignant mesothelioma of the pleura: a survey of 557 cases. Ind Health. 2001;39:161–7.

    Article  CAS  Google Scholar 

  7. Facchetti G, Petrella F, Spaggiari L, Rimoldi I. Malignant pleural mesothelioma: state of the art and advanced cell therapy. Eur J Med Chem. 2017;142:266–70.

    Article  CAS  Google Scholar 

  8. Garcia-Fadrique A, Mehta A, Mohamed F, Dayal S, Cecil T, Moran BJ. Clinical presentation, diagnosis, classification and management of peritoneal mesothelioma: a review. J Gastrointest Oncol. 2017;8:915–24.

    Article  Google Scholar 

  9. Hirasawa A, Imoto I, Naruto T, Akahane T, Yamagami W, Nomura H, Masuda K, Susumu N, Tsuda H, Aoki D. Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer. Oncotarget. 2017;8:112258–67.

    Article  Google Scholar 

  10. Mardis ER. Next-generation DNA sequencing methods. Annu Rev Genomics Hum Genet. 2008;9:387–402.

    Article  CAS  Google Scholar 

  11. Wang J, Wang W, Li R, Li Y, Tian G, Goodman L, Fan W, Zhang J, Li J, Zhang J, et al. The diploid genome sequence of an Asian individual. Nature. 2008;456:60–5.

    Article  CAS  Google Scholar 

  12. Wheeler DA, Srinivasan M, Egholm M, Shen Y, Chen L, McGuire A, He W, Chen YJ, Makhijani V, Roth GT, et al. The complete genome of an individual by massively parallel DNA sequencing. Nature. 2008;452:872–6.

    Article  CAS  Google Scholar 

  13. Yoshii Y, Furukawa T, Waki A, Okuyama H, Inoue M, Itoh M, Zhang MR, Wakizaka H, Sogawa C, Kiyono Y, et al. High-throughput screening with nanoimprinting 3D culture for efficient drug development by mimicking the tumor environment. Biomaterials. 2015;51:278–89.

    Article  CAS  Google Scholar 

  14. Fogh J, Fogh JM, Orfeo T. One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. J Natl Cancer Inst. 1977;59:221–6.

    Article  CAS  Google Scholar 

  15. Shaw TJ, Senterman MK, Dawson K, Crane CA, Vanderhyden BC. Characterization of intraperitoneal, orthotopic, and metastatic xenograft models of human ovarian cancer. Mol Ther. 2004;10:1032–42.

    Article  CAS  Google Scholar 

  16. Hamilton TC, Young RC, McKoy WM, Grotzinger KR, Green JA, Chu EW, Whang-Peng J, Rogan AM, Green WR, Ozols RF. Characterization of a human ovarian carcinoma cell line (NIH:OVCAR-3) with androgen and estrogen receptors. Cancer Res. 1983;43:5379–89.

    CAS  PubMed  Google Scholar 

  17. Tange T, Hasegawa Y, Oka T, Sunaga S, Higashihara M, Matsuo K, Miyazaki H, Shimosaka A, Okano A, Todokoro K. Establishment and characterization of a new human mesothelioma cell line (T-85) from malignant peritoneal mesothelioma with remarkable thrombocytosis. Pathol Int. 1995;45:791–800.

    Article  CAS  Google Scholar 

  18. Oumi N, Itamochi H, Komatsu H, Oishi T, Shimada M, Sato S, Chikumi J, Sato S, Nonaka M, Kudoh A, Harada T. Establishment and mutation analysis of a novel malignant peritoneal mesothelioma cell line, TU-MM-1, using whole genome sequencing. Hum Cell. 2016;29:46–51.

    Article  CAS  Google Scholar 

  19. Li Q, Verschraegen CF, Mendoza J, Hassan R. Cytotoxic activity of the recombinant anti-mesothelin immunotoxin, SS1 (dsFv) PE38, towards tumor cell lines established from ascites of patients with peritoneal mesotheliomas. Anticancer Res. 2004;24:1327–35.

    CAS  PubMed  Google Scholar 

  20. Attanoos RL, Churg A, Galateau-Salle F, Gibbs AR, Roggli VL. Malignant mesothelioma and its non-asbestos causes. Arch Pathol Lab Med. 2018;142:753–60.

    Article  CAS  Google Scholar 

  21. https://www.mhlw.go.jp/toukei/saikin/hw/jinkou/tokusyu/chuuhisyu15/dl/chuuhisyu.pdf. Accessed 27 May 2019.

  22. Gneral rules for clinical and pathological record of mesothelial tumors November 2018 (The 1st Edition) Japan asbestos mesothelioma study group, Japan mesothelioma interest group, the Japan lung cancer society. Kanehara & CO., Ltd., Tokyo, JAPAN, 2018.11

  23. Antoni D, Burckel H, Josset E, Noel G. Three-dimensional cell culture: a breakthrough in vivo. Int J Mol Sci. 2015;16:5517–27.

    Article  CAS  Google Scholar 

  24. Nabavi N, Wei J, Lin D, Collins CC, Gout PW, Wang Y. Pre-clinical models for malignant mesothelioma research: from chemical-induced to patient-derived cancer xenografts. Front Genet. 2018;9:232.

    Article  Google Scholar 

  25. Morotti M, Valenzano Menada M, Venturini PL, Mammoliti S, Ferrero S. Pemetrexed disodium in ovarian cancer treatment. Expert Opin Investig Drugs. 2012;21:437–49.

    Article  CAS  Google Scholar 

  26. Roche M, Parisi L, Li L, Knehans A, Phaeton R, Kesterson JP. The role of pemetrexed in recurrent epithelial ovarian cancer: a scoping review. Oncol Rev. 2018;12:346.

    Article  Google Scholar 

  27. Janne PA, Wozniak AJ, Belani CP, Keohan ML, Ross HJ, Polikoff JA, Mintzer DM, Ye Z, Monberg MJ, Obasaju CK. Pemetrexed expanded access program i: pemetrexed alone or in combination with cisplatin in previously treated malignant pleural mesothelioma: outcomes from a phase IIIB expanded access program. J Thorac Oncol. 2006;1:506–12.

    Article  Google Scholar 

  28. van den Bogaert DP, Pouw EM, van Wijhe G, Vernhout RM, Surmont VF, Hoogsteden HC, van Klaveren RJ. Pemetrexed maintenance therapy in patients with malignant pleural mesothelioma. J Thorac Oncol. 2006;1:25–30.

    Article  Google Scholar 

  29. Scherpereel A, Mazieres J, Greillier L, Lantuejoul S, Do P, Bylicki O, Monnet I, Corre R, Audigier-Valette C, Locatelli-Sanchez M, et al. Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): a multicentre, open-label, randomised, non-comparative, phase 2 trial. Lancet Oncol. 2019;20:239–53.

    Article  CAS  Google Scholar 

  30. Hassan R, Alley E, Kindler H, Antonia S, Jahan T, Honarmand S, Nair N, Whiting CC, Enstrom A, Lemmens E, et al: Live-Attenuated, Listeria monocytogenes Expressing Mesothelin (CRS-207) with Chemotherapy for Treatment of Malignant Pleural Mesothelioma. Clin Cancer Res 2019.

  31. Papa S, Popat S, Shah R, Prevost AT, Lal R, McLennan B, Cane P, Lang-Lazdunski L, Viney Z, Dunn JT, et al. Phase 2 study of sorafenib in malignant mesothelioma previously treated with platinum-containing chemotherapy. J Thorac Oncol. 2013;8:783–7.

    Article  CAS  Google Scholar 

  32. Dubey S, Janne PA, Krug L, Pang H, Wang X, Heinze R, Watt C, Crawford J, Kratzke R, Vokes E, Kindler HL. A phase II study of sorafenib in malignant mesothelioma: results of Cancer and Leukemia Group B 30307. J Thorac Oncol. 2010;5:1655–61.

    Article  Google Scholar 

  33. Ugurluer G, Chang K, Gamez ME, Arnett AL, Jayakrishnan R, Miller RC, Sio TT. Genome-based mutational analysis by next generation sequencing in patients with malignant pleural and peritoneal mesothelioma. Anticancer Res. 2016;36:2331–8.

    CAS  PubMed  Google Scholar 

  34. Bueno R, Stawiski EW, Goldstein LD, Durinck S, De Rienzo A, Modrusan Z, Gnad F, Nguyen TT, Jaiswal BS, Chirieac LR, et al. Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations. Nat Genet. 2016;48:407–16.

    Article  CAS  Google Scholar 

  35. Betti M, Aspesi A, Biasi A, Casalone E, Ferrante D, Ogliara P, Gironi LC, Giorgione R, Farinelli P, Grosso F, et al. CDKN2A and BAP1 germline mutations predispose to melanoma and mesothelioma. Cancer Lett. 2016;378:120–30.

    Article  CAS  Google Scholar 

  36. Testa JR, Cheung M, Pei J, Below JE, Tan Y, Sementino E, Cox NJ, Dogan AU, Pass HI, Trusa S, et al. Germline BAP1 mutations predispose to malignant mesothelioma. Nat Genet. 2011;43:1022–5.

    Article  CAS  Google Scholar 

  37. Ohar JA, Cheung M, Talarchek J, Howard SE, Howard TD, Hesdorffer M, Peng H, Rauscher FJ, Testa JR. Germline BAP1 mutational landscape of asbestos-exposed malignant mesothelioma patients with family history of cancer. Cancer Res. 2016;76:206–15.

    Article  CAS  Google Scholar 

  38. Haugh AM, Njauw CN, Bubley JA, Verzi AE, Zhang B, Kudalkar E, VandenBoom T, Walton K, Swick BL, Kumar R, et al. Genotypic and phenotypic features of BAP1 cancer syndrome: a report of 8 new families and review of cases in the literature. JAMA Dermatol. 2017;153:999–1006.

    Article  Google Scholar 

  39. Husain AN, Colby TV, Ordonez NG, Allen TC, Attanoos RL, Beasley MB, Butnor KJ, Chirieac LR, Churg AM, Dacic S, et al. Guidelines for pathologic diagnosis of malignant mesothelioma 2017 update of the consensus statement from the international mesothelioma interest group. Arch Pathol Lab Med. 2018;142:89–108.

    Article  CAS  Google Scholar 

  40. Prat J. Ovarian carcinomas: five distinct diseases with different origins, genetic alterations, and clinicopathological features. Virchows Arch. 2012;460:237–49.

    Article  Google Scholar 

Download references

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).

Author information

Author notes

  1. Tomoko Akahane, Akira Hirasawa, and Issei Imoto contributed equally to this work.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Tomoko Akahane, Akira Hirasawa, Yoshiko Nanki, Tomoko Yoshihama, Eichiro Tominaga & Daisuke Aoki

  2. Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan

    Akira Hirasawa

  3. Division of Molecular Genetics, Aichi Cancer Center Research Institute, Nagoya, Japan

    Issei Imoto

  4. Division of Cancer Genetics, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Issei Imoto

  5. JSR Corporation, Tokyo, Japan

    Aki Okubo & Manabu Itoh

Authors
  1. Tomoko Akahane
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akira Hirasawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Issei Imoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aki Okubo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Manabu Itoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yoshiko Nanki
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tomoko Yoshihama
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Eichiro Tominaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Daisuke Aoki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tomoko Akahane.

Ethics declarations

Conflicts of interest

We have no conflicts of interest to declare for this study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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). https://doi.org/10.1007/s13577-019-00286-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-019-00286-w

Keywords

Search

Navigation