Anirban K Mitra1, David A Davis2, Sunil Tomar1, Lynn Roy3, Hilal Gurler4, Jia Xie4, Daniel D Lantvit2, Horacio Cardenas5, Fang Fang1, Yueying Liu6, Elizabeth Loughran6, Jing Yang6, M Sharon Stack6, Robert E Emerson7, Karen D Cowden Dahl8, Maria V Barbolina4, Kenneth P Nephew9, Daniela Matei5, Joanna E Burdette2. 1. Medical Sciences Program, Indiana University School of Medicine, Indiana University, Bloomington, IN, United States. 2. Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL, United States. 3. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine-South Bend; Harper Cancer Research Institute, Notre Dame, IN. 4. Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL, United States. 5. Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States. 6. Harper Cancer Research Institute, Notre Dame, IN; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, United States. 7. Department of Pathology Indiana University School of Medicine, Indianapolis, IN, United States. 8. 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. 9. 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.
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.
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.
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