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

doi:10.1007/s13577-017-0162-1

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

Hum Cell. 2017 Jul;30(3):226-236. doi: 10.1007/s13577-017-0162-1. Epub 2017 Mar 1.

Authors

Pang-Ning Teng¹, Nicholas W Bateman^{1

2

3}, Guisong Wang¹, Tracy Litzi¹, Brian E Blanton¹, Brian L Hood¹, Kelly A Conrads¹, Wei Ao¹, Kate E Oliver⁴, Kathleen M Darcy^{1

2}, William P McGuire⁵, Keren Paz⁶, David Sidransky⁷, Chad A Hamilton^{1

2

4}, G Larry Maxwell^{1

2

8

9}, Thomas P Conrads^{10

11

12

13

14}

Affiliations

¹ Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale, VA, USA.
² The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, MD, USA.
³ Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
⁴ Gynecologic Oncology Service, Department of Obstetrics and Gynecology, Walter Reed National Military Medical Center, Bethesda, MD, USA.
⁵ Department of Internal Medicine, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
⁶ Champions Oncology, Inc., Baltimore, MD, USA.
⁷ Otolaryngology-Head and Neck Surgery and Oncology, Johns Hopkins University, Baltimore, MD, USA.
⁸ Department of Obstetrics and Gynecology, Inova Fairfax Hospital, Falls Church, VA, USA.
⁹ Inova Schar Cancer Institute, Inova Center for Personalized Health, Falls Church, VA, USA.
¹⁰ Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale, VA, USA. [email protected].
¹¹ The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, MD, USA. [email protected].
¹² Department of Obstetrics and Gynecology, Inova Fairfax Hospital, Falls Church, VA, USA. [email protected].
¹³ Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. [email protected].
¹⁴ Inova Schar Cancer Institute, Inova Center for Personalized Health, Falls Church, VA, USA. [email protected].

PMID: 28251557
DOI: 10.1007/s13577-017-0162-1

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.

Keywords: Cell line; High grade serous; Ovarian cancer; Paclitaxel resistance; Platinum resistance.

MeSH terms

Animals
Antineoplastic Agents / pharmacology*
Carboplatin / pharmacology*
Carcinoma / genetics
Carcinoma / pathology*
Cell Line, Tumor
Cisplatin / pharmacology*
Dose-Response Relationship, Drug
Drug Discovery
Drug Resistance, Neoplasm*
Exome / genetics
Female
Gene Expression Profiling
Heterografts
Humans
Mice
Mutation
Neoplasm Staging
Neoplasm Transplantation
Ovarian Neoplasms / genetics
Ovarian Neoplasms / pathology*
Paclitaxel / pharmacology*
Proteomics
Tumor Suppressor Protein p53 / genetics

Substances

Antineoplastic Agents
TP53 protein, human
Tumor Suppressor Protein p53
Carboplatin
Paclitaxel
Cisplatin