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. 2015 Aug;138(2):372-7.
doi: 10.1016/j.ygyno.2015.05.040. Epub 2015 Jun 5.

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

Anirban K Mitra  1 , David A Davis  2 , Sunil Tomar  1 , Lynn Roy  3 , Hilal Gurler  4 , Jia Xie  4 , Daniel D Lantvit  2 , Horacio Cardenas  5 , Fang Fang  1 , Yueying Liu  6 , Elizabeth Loughran  6 , Jing Yang  6 , M Sharon Stack  6 , Robert E Emerson  7 , Karen D Cowden Dahl  8 , Maria V Barbolina  4 , Kenneth P Nephew  9 , Daniela Matei  5 , Joanna E Burdette  2
Affiliations

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

Anirban K Mitra et al. Gynecol Oncol. 2015 Aug.

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.

Keywords: High grade serous ovarian cancer; Mouse model; Pax8; Xenograft.

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Figures

Figure 1
Figure 1
Average tumor weight. Animals were sacrificed at 90 days unless tumor burden required euthanasia at an earlier time point (summarized in Table 1). Most cell models formed both intraperitoneal (i.p.; left) and subcutaneous (s.c.; right) tumors, but OVSAHO only formed IP and OVKATE and COV362 only formed SC.
Figure 2
Figure 2
Intraperitoneal (i.p.) dissemination of ovarian cancer cell lines in athymic nude mice. Cell models demonstrated unique sites of colonization (summarized in Table 2). Pictures are shown at time of dissection from a representative mouse with i.p. tumors
Figure 3
Figure 3
Human ovarian cancer cell models form high-grade serous tumors based on histology and protein expression. Cell models that formed intraperitoneal tumors are shown except for OVKATE and COV362, which only grew subcutaneous tumors. Histology and immunohistochemical staining of PAX8, WT1, and p53 are shown for human cell models. Scale bars equal 50 microns.
See this image and copyright information in PMC

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