title: Establishment and characterization of a platinum- and paclitaxel-resistant high grade serous ovarian carcinoma cell line.
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.
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale, VA, USA.
authors.forename: Pang-Ning
authors.initials: PN
authors.lastname: Teng
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale, VA, USA.|The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, MD, USA.|Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Bateman
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale, VA, USA.
authors.forename: Guisong
authors.initials: G
authors.lastname: Wang
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale, VA, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Litzi
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale, VA, USA.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Blanton
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale, VA, USA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Hood
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale, VA, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Conrads
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale, VA, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Ao
authors.affiliation: Gynecologic Oncology Service, Department of Obstetrics and Gynecology, Walter Reed National Military Medical Center, Bethesda, MD, USA.
authors.forename: Kate E
authors.initials: KE
authors.lastname: Oliver
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale, VA, USA.|The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, MD, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Darcy
authors.affiliation: Department of Internal Medicine, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: William P
authors.initials: WP
authors.lastname: McGuire
authors.affiliation: Champions Oncology, Inc., Baltimore, MD, USA.
authors.forename: Keren
authors.initials: K
authors.lastname: Paz
authors.affiliation: Otolaryngology-Head and Neck Surgery and Oncology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale, VA, USA.|The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, MD, USA.|Gynecologic Oncology Service, Department of Obstetrics and Gynecology, Walter Reed National Military Medical Center, Bethesda, MD, USA.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Hamilton
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale, VA, USA.|The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, MD, USA.|Department of Obstetrics and Gynecology, Inova Fairfax Hospital, Falls Church, VA, USA.|Inova Schar Cancer Institute, Inova Center for Personalized Health, Falls Church, VA, USA.
authors.forename: G Larry
authors.initials: GL
authors.lastname: Maxwell
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale, VA, USA. thomas.conrads@inova.org.|The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, MD, USA. thomas.conrads@inova.org.|Department of Obstetrics and Gynecology, Inova Fairfax Hospital, Falls Church, VA, USA. thomas.conrads@inova.org.|Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. thomas.conrads@inova.org.|Inova Schar Cancer Institute, Inova Center for Personalized Health, Falls Church, VA, USA. thomas.conrads@inova.org.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Conrads
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016190:Carboplatin / Q000494:pharmacology*; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D019008:Drug Resistance, Neoplasm; D059472:Exome / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D064593:Heterografts; D006801:Humans; D051379:Mice; D009154:Mutation; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology*; D040901:Proteomics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin
keywords: Cell line; High grade serous; Ovarian cancer; Paclitaxel resistance; Platinum resistance