Establishment and characterization of a platinum- and paclitaxel-resistant high grade serous ovarian carcinoma cell line

Pang Ning Teng, Nicholas W. Bateman, Guisong Wang, Tracy Litzi, Brian E. Blanton, Brian L. Hood, Kelly A. Conrads, Wei Ao, Kate E. Oliver, Kathleen M. Darcy, William P. McGuire, Keren Paz, David Sidransky, Chad A. Hamilton, G. Larry Maxwell, Thomas P. Conrads

Research output: Contribution to journalArticlepeer-review

Abstract

High grade serous ovarian cancer (HGSOC) patients have a high recurrence rate after surgery and adjuvant chemotherapy due to inherent or acquired drug resistance. Cell lines derived from HGSOC tumors that are resistant to chemotherapeutic agents represent useful pre-clinical models for drug discovery. Here, we describe establishment of a human ovarian carcinoma cell line, which we term WHIRC01, from a patient-derived mouse xenograft established from a chemorefractory HGSOC patient who did not respond to carboplatin and paclitaxel therapy. This newly derived cell line is platinum- and paclitaxel-resistant with cisplatin, carboplatin, and paclitaxel half-maximal lethal doses of 15, 130, and 20 µM, respectively. Molecular characterization of this cell line was performed using targeted DNA exome sequencing, transcriptomics (RNA-seq), and mass spectrometry-based proteomic analyses. Results from exomic sequencing revealed mutations in TP53 consistent with HGSOC. Transcriptomic and proteomic analyses of WHIRC01 showed high level of alpha-enolase and vimentin, which are associated with cell migration and epithelial–mesenchymal transition. WHIRC01 represents a chemorefractory human HGSOC cell line model with a comprehensive molecular profile to aid future investigations of drug resistance mechanisms and screening of chemotherapeutic agents.

Original languageEnglish (US)
Pages (from-to)226-236
Number of pages11
JournalHuman Cell
Volume30
Issue number3
DOIs
StatePublished - Jul 1 2017

Keywords

  • Cell line
  • High grade serous
  • Ovarian cancer
  • Paclitaxel resistance
  • Platinum resistance

ASJC Scopus subject areas

  • Cell Biology
  • Cancer Research

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