期刊
GYNECOLOGIC ONCOLOGY
卷 139, 期 1, 页码 97-103出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygyno.2015.08.017
关键词
Ovarian cancer; Cell line model; Xenograft; Genomics
资金
- Ruth N. White Research Fellowship in Gynecologic Oncology
- Sperling Family Fund Fellowship
- Robert and Deborah First Fund
- Ruth L. Kirschstein National Research Service Award [F31-CA176995-01A1]
- National Cancer Institute at the NIH [P50-CA083636]
- NIH [U01-CA152990, R21-CA156021, CA121113]
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- Honorable Tina Brozman Foundation
- Gamel Family Ovarian Cancer Research Fund
- Commonwealth Foundation
Objective. Comparisons of The Cancer Genome Atlas (TCGA) with high grade serous ovarian cancer (HGSOC) cell lines used in research reveal that many common experimental models lack defining genomic characteristics seen in patient tumors. As cell lines exist with higher genomic fidelity to TCGA, this study aimed to evaluate the utility of these cell lines as tools for preclinical investigation. Methods. We compared two HGSOC cell lines with supposed high genomic fidelity to TCGA, KURAMOCHI and OVSAHO, with the most commonly cited ovarian cancer cell line, SKOV3, which has poor genomic fidelity to TCGA. The lines were analyzed for genomic alterations, in vitro performance, and growth in murine xenografts. Results. Using targeted next generation sequencing analyses, we determined that each line had a distinct mutation profile, including alterations in TP53, and copy number variation of specific genes. KURAMOCHI and OVSAHO better recapitulated serous carcinoma morphology than SKOV3. All lines expressed PAX8 and stathmin, but KURAMOCHI and OVSAHO did not express CK7. KURAMOCHI was significantly more platinum sensitive than OVSAHO and SKOV3. Unlike SKOV3, KURAMOCHI and OVSAHO engrafted poorly in subcutaneous xenografts. KURAMOCHI and OVSAHO grew best after intraperitoneal injection in SCID mice and recapitulated miliary disease while SKOV3 grew in all murine systems and formed oligometastatic disease. Conclusions. The research utility of HGSOC cell line models requires a comprehensive assessment of genomic as well as in vitro and in vivo properties. Cell lines with closer genomic fidelity to human tumors may have limitations in performance for preclinical investigation. (C) 2015 Elsevier Inc. All rights reserved.
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