In vivo tumor growth of high-grade serous ovarian cancer cell lines

Anirban K. Mitra*, David A. Davis, Sunil Tomar, Lynn Roy, Hilal Gurler, Jia Xie, Daniel D. Lantvit, Horacio Cardenas, Fang Fang, Yueying Liu, Elizabeth Loughran, Jing Yang, M. Sharon Stack, Robert E. Emerson, Karen D. Cowden Dahl, Maria V. Barbolina, Kenneth P. Nephew, Daniela Matei, Joanna E. Burdette

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

154 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)372-377
Number of pages6
JournalGynecologic oncology
Volume138
Issue number2
DOIs
StatePublished - Aug 1 2015

Funding

The authors thank Sue Childress and Jay Pilrose for technical assistance. This work was supported in part by grants RSG-12-230-01-TBG from the American Cancer Society Illinois Division and DOD OCRP OC130046 (JEB), the Ovarian Cancer Research Foundation Liz Tilberis Scholar Award (MVB, JEB, and KCD), NIH/NCI grants CA109545 (MSS) and CA086984 (MSS), V Foundation and NIH/NCI CA182832 (DM and KPN), and NSF DGE1313583 (EL). We would like to acknowledge the generous donation from Adam Karpf of the COV362 cell line.

Keywords

  • High grade serous ovarian cancer
  • Mouse model
  • Pax8
  • Xenograft

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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