2. Academic Validation
  3. Characterization of Mutational Status, Spheroid Formation, and Drug Response of a New Genomically-Stable Human Ovarian Clear Cell Carcinoma Cell Line, 105C

Characterization of Mutational Status, Spheroid Formation, and Drug Response of a New Genomically-Stable Human Ovarian Clear Cell Carcinoma Cell Line, 105C

  • Cells. 2020 Nov 3;9(11):2408. doi: 10.3390/cells9112408.
Bart Kolendowski 1 2,  Yudith Ramos Valdes 1 2,  Hal Hirte 3,  Hiroaki Itamochi 4,  Wonjae Lee 1 2 5,  Mark Carey 6,  Trevor G Shepherd 1 2 7 8 9,  Gabriel E DiMattia 1 2 7 10
Affiliations

Affiliations

  • 1 Mary & John Knight Translational Ovarian Cancer Research Unit, London Regional Cancer Program, London, ON N6A 5W9, Canada.
  • 2 Lawson Health Research Institute, London, ON N6C 2R5, Canada.
  • 3 Juravinski Cancer Centre, Hamilton, ON L8V 5C2, Canada.
  • 4 Department of Obstetrics and Gynecology, Tottori University School of Medicine, Nishi-cho, Yonago-shi, Tottori-ken 683-0826, Japan.
  • 5 Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON L8P 1H6, Canada.
  • 6 Department of Obstetrics & Gynaecology, University of British Columbia, Vancouver, BC V6Z 2K8, Canada.
  • 7 Department of Oncology, Western University, London, ON N6A 5W9, Canada.
  • 8 Department of Anatomy & Cell Biology, Western University, London, ON N6A 3K7, Canada.
  • 9 Department of Obstetrics & Gynaecology, Western University, London, ON N6H 5W9, Canada.
  • 10 Department of Biochemistry, Western University, London, ON N6A 5C1, Canada.
PMID: 33153119 DOI: 10.3390/cells9112408
Abstract

Ovarian clear cell carcinoma (OCCC) is a rare subtype of gynecological Cancer for which well-characterized and authenticated model systems are scarce. We provide an extensive characterization of '105C', a cell line generated from an adenocarcinoma of the clear cell histotype using targeted next-generation sequencing, cytogenetic microarrays, along with analyses of Akt/mTOR signaling. We report that that the 105C cell line is a bona fide OCCC cell line, carrying PIK3CA, PTEN, and ARID1A gene mutations, consistent with OCCC, yet maintain a stable genome as reflected by low copy number variation. Unlike KOC-7c, TOV-21G, and RMG-V OCCC lines also mutated for the above genes, the 105C cells do not carry mutations in mismatch repair genes. Importantly, we show that 105C cells exhibit greater resistance to mTOR inhibition and carboplatin treatment compared to 9 other OCCC cell lines in 3D spheroid cultures. This resistance may be attributed to 105C cells remaining dormant in suspension culture which surprisingly, contrasts with several other OCCC lines which continue to proliferate in long-term suspension culture. 105C cells survive xenotransplantation but do not proliferate and metastasize. Collectively, we show that the 105C OCCC cell line exhibits unique properties useful for the pre-clinical investigation of OCCC pathobiology.

Keywords

OCCC; cancer; cell line; clear cell; epithelial ovarian cancer; mTOR inhibitor; ovarian; spheroid.

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