title: In vivo tumor growth of high-grade serous ovarian cancer cell lines.
abstract: OBJECTIVE
  Genomic studies of ovarian cancer (OC) cell lines frequently used in research revealed that these cells do not fully represent high-grade serous ovarian cancer (HGSOC), the most common OC histologic type. However, OC lines that appear to genomically resemble HGSOC have not been extensively used and their growth characteristics in murine xenografts are essentially unknown.
  
  
  METHODS
  To better understand growth patterns and characteristics of HGSOC cell lines in vivo, CAOV3, COV362, KURAMOCHI, NIH-OVCAR3, OVCAR4, OVCAR5, OVCAR8, OVSAHO, OVKATE, SNU119 and UWB1.289 cells were assessed for tumor formation in nude mice. Cells were injected intraperitoneally (i.p.) or subcutaneously (s.c.) in female athymic nude mice and allowed to grow (maximum of 90 days) and tumor formation was analyzed. All tumors were sectioned and assessed using H&E staining and immunohistochemistry for p53, PAX8 and WT1 expression.
  
  
  RESULTS
  Six lines (OVCAR3, OVCAR4, OVCAR5, OVCAR8, CAOV3, and OVSAHO) formed i.p xenografts with HGSOC histology. OVKATE and COV362 formed s.c. tumors only. Rapid tumor formation was observed for OVCAR3, OVCAR5 and OVCAR8, but only OVCAR8 reliably formed ascites. Tumors derived from OVCAR3, OVCAR4, and OVKATE displayed papillary features. Of the 11 lines examined, three (Kuramochi, SNU119 and UWB1.289) were non-tumorigenic.
  
  
  CONCLUSIONS
  Our findings help further define which HGSOC cell models reliably generate tumors and/or ascites, critical information for preclinical drug development, validating in vitro findings, imaging and prevention studies by the OC research community.
authors.affiliation: Medical Sciences Program, Indiana University School of Medicine, Indiana University, Bloomington, IN, United States.
authors.forename: Anirban K
authors.initials: AK
authors.lastname: Mitra
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Davis
authors.affiliation: Medical Sciences Program, Indiana University School of Medicine, Indiana University, Bloomington, IN, United States.
authors.forename: Sunil
authors.initials: S
authors.lastname: Tomar
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine-South Bend; Harper Cancer Research Institute, Notre Dame, IN.
authors.forename: Lynn
authors.initials: L
authors.lastname: Roy
authors.affiliation: Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL, United States.
authors.forename: Hilal
authors.initials: H
authors.lastname: Gurler
authors.affiliation: Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL, United States.
authors.forename: Jia
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL, United States.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Lantvit
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States.
authors.forename: Horacio
authors.initials: H
authors.lastname: Cardenas
authors.affiliation: Medical Sciences Program, Indiana University School of Medicine, Indiana University, Bloomington, IN, United States.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Harper Cancer Research Institute, Notre Dame, IN; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, United States.
authors.forename: Yueying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Harper Cancer Research Institute, Notre Dame, IN; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, United States.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Loughran
authors.affiliation: Harper Cancer Research Institute, Notre Dame, IN; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, United States.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Harper Cancer Research Institute, Notre Dame, IN; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, United States.
authors.forename: M
authors.initials: M
authors.lastname: Sharon Stack
authors.affiliation: Department of Pathology Indiana University School of Medicine, Indianapolis, IN, United States.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Emerson
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine-South Bend; Harper Cancer Research Institute, Notre Dame, IN; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, United States.
authors.forename: Karen D
authors.initials: KD
authors.lastname: Cowden Dahl
authors.affiliation: Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL, United States.
authors.forename: Maria
authors.initials: M
authors.lastname: V Barbolina
authors.affiliation: Medical Sciences Program, Indiana University School of Medicine, Indiana University, Bloomington, IN, United States; Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, United States.
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Nephew
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States.
authors.forename: Daniela
authors.initials: D
authors.lastname: Matei
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL, United States.
authors.forename: Joanna E
authors.initials: JE
authors.lastname: Burdette
mesh_terms: D000818:Animals; D048708:Cell Growth Processes; D045744:Cell Line, Tumor; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D025721:WT1 Proteins / Q000096:biosynthesis
chemical_list: D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025721:WT1 Proteins; C583751:WT1 protein, human
keywords: High grade serous ovarian cancer; Mouse model; Pax8; Xenograft