Derivation and characterization of matched cell lines from primary and recurrent serous ovarian cancer
- Equal contributors
1 Centre de recherche du Centre hospitalier de l’Université de Montréal (CHUM)/Institut du cancer de Montréal, Montréal, Canada
2 The Research Institute of the McGill University Health Centre, Montréal, Canada
3 Department of Human Genetics, McGill University, Montréal, Canada
4 Department of Medicine, McGill University, Montréal, Canada
5 Division de gynécologie oncologique, Département d’obstétrique et gynécologie, Université de Montréal, Montréal, Canada
6 Département de médecine, Université de Montréal, Montréal, Canada
BMC Cancer 2012, 12:379 doi:10.1186/1471-2407-12-379Published: 29 August 2012
Cell line models have proven to be effective tools to investigate a variety of ovarian cancer features. Due to the limited number of cell lines, particularly of the serous subtype, the heterogeneity of the disease, and the lack of cell lines that model disease progression, there is a need to further develop cell line resources available for research. This study describes nine cell lines derived from three ovarian cancer cases that were established at initial diagnosis and at subsequent relapse after chemotherapy.
The cell lines from three women diagnosed with high-grade serous ovarian cancer (1369, 2295 and 3133) were derived from solid tumor (TOV) and ascites (OV), at specific time points at diagnosis and relapse (R). Primary treatment was a combination of paclitaxel/carboplatin (1369, 3133), or cisplatin/topotecan (2295). Second line treatment included doxorubicin, gemcitabine and topotecan. In addition to molecular characterization (p53, HER2), the cell lines were characterized based on cell growth characteristics including spheroid growth, migration potential, and anchorage independence. The in vivo tumorigenicity potential of the cell lines was measured. Response to paclitaxel and carboplatin was assessed using a clonogenic assay.
All cell lines had either a nonsense or missense TP53 mutations. The ability to form compact spheroids or aggregates was observed in six of nine cell lines. Limited ability for migration and anchorage independence was observed. The OV3133(R) cell line, formed tumors at subcutaneous sites in SCID mice. Based on IC50 values and dose response curves, there was clear evidence of acquired resistance to carboplatin for TOV2295(R) and OV2295(R2) cell lines.
The study identified nine new high-grade serous ovarian cancer cell lines, derived before and after chemotherapy that provides a unique resource for investigating the evolution of this common histopathological subtype of ovarian cancer.