Characterization of twenty-five ovarian tumour cell lines that phenocopy primary tumours

Currently available human tumour cell line panels consist of a small number of lines in each lineage that generally fail to retain the phenotype of the original patient tumour. Here we develop a cell culture medium that enables us to routinely establish cell lines from diverse subtypes of human ovarian cancers with >95% efficiency. Importantly, the 25 new ovarian tumour cell lines described here retain the genomic landscape, histopathology and molecular features of the original tumours. Furthermore, the molecular profile and drug response of these cell lines correlate with distinct groups of primary tumours with different outcomes. Thus, tumour cell lines derived using this methodology represent a significantly improved platform to study human tumour pathophysiology and response to therapy.

[1]  Craig E. Higgins,et al.  Differential requirement for MEK/ERK and SMAD signaling in PAI-1 and CTGF expression in response to microtubule disruption. , 2009, Cellular signalling.

[2]  W. McCluggage,et al.  Morphological subtypes of ovarian carcinoma: a review with emphasis on new developments and pathogenesis. , 2011, Pathology.

[3]  P. Menéndez,et al.  The ROCK Inhibitor Y-27632 Negatively Affects the Expansion/Survival of Both Fresh and Cryopreserved Cord Blood-Derived CD34+ Hematopoietic Progenitor Cells , 2010, Stem Cell Reviews and Reports.

[4]  G. Lowther,et al.  Long-term culture of primary breast cancer in defined medium , 2005, Breast Cancer Research and Treatment.

[5]  G. Mills,et al.  Mesenchymal gene program-expressing ovarian cancer spheroids exhibit enhanced mesothelial clearance. , 2014, The Journal of clinical investigation.

[6]  J. Bertoglio,et al.  Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing , 2001, Nature Cell Biology.

[7]  Kakajan Komurov,et al.  Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes , 2010, Proceedings of the National Academy of Sciences.

[8]  James D Iglehart,et al.  Transformation of different human breast epithelial cell types leads to distinct tumor phenotypes. , 2007, Cancer cell.

[9]  M. Köbel,et al.  Ovarian carcinoma histotype determination is highly reproducible, and is improved through the use of immunohistochemistry , 2014, Histopathology.

[10]  Susan Band Horwitz,et al.  Mechanisms of Taxol resistance related to microtubules , 2003, Oncogene.

[11]  J. Campisi Cell biology: The beginning of the end , 2013, Nature.

[12]  B. Têtu,et al.  Gene expression profiling of paired ovarian tumors obtained prior to and following adjuvant chemotherapy: molecular signatures of chemoresistant tumors. , 2006, International journal of oncology.

[13]  Dennis C. Sgroi,et al.  Integrins and EGFR coordinately regulate the pro-apoptotic protein Bim to prevent anoikis , 2003, Nature Cell Biology.

[14]  D. Amadori,et al.  Establishment and characterization of a new cell line from primary human breast carcinoma , 2004, Breast Cancer Research and Treatment.

[15]  John Quackenbush,et al.  Gene Expression Signature of Normal Cell-of-Origin Predicts Ovarian Tumor Outcomes , 2013, PloS one.

[16]  Hiroshi Iwasaki,et al.  CD133+ Cancer Stem Cell–like Cells Derived from Uterine Carcinosarcoma (Malignant Mixed Müllerian Tumor) , 2011, Stem cells.

[17]  Terence P. Speed,et al.  A comparison of normalization methods for high density oligonucleotide array data based on variance and bias , 2003, Bioinform..

[18]  R. Drapkin,et al.  The distal fallopian tube: a new model for pelvic serous carcinogenesis , 2007, Current opinion in obstetrics & gynecology.

[19]  J. Boyd,et al.  Gene Expression Profiles of Serous, Endometrioid, and Clear Cell Subtypes of Ovarian and Endometrial Cancer , 2005, Clinical Cancer Research.

[20]  T. Speed,et al.  Summaries of Affymetrix GeneChip probe level data. , 2003, Nucleic acids research.

[21]  Kenneth P. Nephew,et al.  Rethinking ovarian cancer: recommendations for improving outcomes , 2011, Nature Reviews Cancer.

[22]  S. Cook,et al.  Activation of the ERK1/2 Signaling Pathway Promotes Phosphorylation and Proteasome-dependent Degradation of the BH3-only Protein, Bim* , 2003, Journal of Biological Chemistry.

[23]  Luis Chiriboga,et al.  Expression of Pax8 as a Useful Marker in Distinguishing Ovarian Carcinomas From Mammary Carcinomas , 2008, The American journal of surgical pathology.

[24]  Kathleen R. Cho,et al.  Ovarian cancer update: lessons from morphology, molecules, and mice. , 2009, Archives of pathology & laboratory medicine.

[25]  C. Roberts,et al.  ARID1A mutations in cancer: another epigenetic tumor suppressor? , 2013, Cancer discovery.

[26]  G. Mills,et al.  Reverse phase protein array: validation of a novel proteomic technology and utility for analysis of primary leukemia specimens and hematopoietic stem cells , 2006, Molecular Cancer Therapeutics.

[27]  C. Huttenhower,et al.  Risk prediction for late-stage ovarian cancer by meta-analysis of 1525 patient samples. , 2014, Journal of the National Cancer Institute.

[28]  J. Troge,et al.  Tumour evolution inferred by single-cell sequencing , 2011, Nature.

[29]  J. Troge,et al.  Inferring tumor progression from genomic heterogeneity. , 2010, Genome research.

[30]  American Type Culture Collection Standards Development Orga ASN-0002 Cell line misidentification: the beginning of the end , 2010, Nature Reviews Cancer.

[31]  Endothelial-like properties of claudin-low breast cancer cells promote tumor vascular permeability and metastasis , 2013, Clinical & Experimental Metastasis.

[32]  Michael M Gottesman,et al.  Cisplatin Resistance: A Cellular Self-Defense Mechanism Resulting from Multiple Epigenetic and Genetic Changes , 2012, Pharmacological Reviews.

[33]  Alexander Kamb,et al.  What's wrong with our cancer models? , 2005, Nature Reviews Drug Discovery.

[34]  Kathleen R. Cho,et al.  Mouse model of human ovarian endometrioid adenocarcinoma based on somatic defects in the Wnt/beta-catenin and PI3K/Pten signaling pathways. , 2007, Cancer cell.

[35]  S. Leung,et al.  Calculator for ovarian carcinoma subtype prediction , 2011, Modern Pathology.

[36]  A. Whittemore,et al.  Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study. , 2013, The Lancet. Oncology.

[37]  R. Tothill,et al.  Novel Molecular Subtypes of Serous and Endometrioid Ovarian Cancer Linked to Clinical Outcome , 2008, Clinical Cancer Research.

[38]  K. Coombes,et al.  Clinical evaluation of chemotherapy response predictors developed from breast cancer cell lines , 2010, Breast Cancer Research and Treatment.

[39]  S. Nishikawa,et al.  A ROCK inhibitor permits survival of dissociated human embryonic stem cells , 2007, Nature Biotechnology.

[40]  A. Krasinskas,et al.  NY-BR-1 and PAX8 immunoreactivity in breast, gynecologic tract, and other CK7+ carcinomas: potential use for determining site of origin. , 2011, American journal of clinical pathology.

[41]  M. Olivé,et al.  Long-term human breast carcinoma cell lines of metastatic origin: Preliminary characterization , 1978, In Vitro.

[42]  M. Westerfield,et al.  Characterization of paired tumor and non‐tumor cell lines established from patients with breast cancer , 1998, International journal of cancer.

[43]  J. Ford A beginning or an end? , 1987, Nature.

[44]  S. Shah,et al.  Type-Specific Cell Line Models for Type-Specific Ovarian Cancer Research , 2013, PloS one.

[45]  S. Canevari,et al.  The value of PAX8 and WT1 molecules in ovarian cancer diagnosis. , 2013, Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie.

[46]  Chris Albanese,et al.  ROCK inhibitor and feeder cells induce the conditional reprogramming of epithelial cells. , 2012, The American journal of pathology.

[47]  G. Pagès,et al.  Phosphorylation of Bim-EL by Erk1/2 on serine 69 promotes its degradation via the proteasome pathway and regulates its proapoptotic function , 2003, Oncogene.

[48]  B. Bryan,et al.  Pharmacological inhibition of Rho-kinase signaling with Y-27632 blocks melanoma tumor growth. , 2010, Oncology reports.

[49]  R. Bast,et al.  Establishment and characterization of cancer cell cultures and xenografts derived from primary or metastatic Mullerian cancers. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[50]  H. Höfler,et al.  Intratumoral heterogeneity in breast carcinoma revealed by laser-microdissection and comparative genomic hybridization. , 1999, Cancer genetics and cytogenetics.

[51]  Benjamin Frederick Ganzfried,et al.  Comparative meta-analysis of prognostic gene signatures for late-stage ovarian cancer. , 2014, Journal of the National Cancer Institute.

[52]  A. Paradiso,et al.  Preferential chemosensitization of PTEN‐mutated prostate cells by silencing the Akt kinase , 2007, The Prostate.

[53]  D. Hancock,et al.  Role of Bim in the survival pathway induced by Raf in epithelial cells , 2004, Oncogene.

[54]  P. Yelick,et al.  Cytogenetic instability of dental pulp stem cell lines , 2012, Journal of Molecular Histology.

[55]  L. Seymour,et al.  Clinical predictive value of the in vitro cell line, human xenograft, and mouse allograft preclinical cancer models. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[56]  K. Cibulskis,et al.  Prognostically relevant gene signatures of high-grade serous ovarian carcinoma. , 2012, The Journal of clinical investigation.

[57]  E Y LASFARGUES,et al.  Cultivation of human breast carcinomas. , 1958, Journal of the National Cancer Institute.

[58]  J. Aster,et al.  Defined, serum-free conditions for in vitro culture of primary human T-ALL blasts , 2012, Leukemia.

[59]  C. Sander,et al.  Evaluating cell lines as tumour models by comparison of genomic profiles , 2013, Nature Communications.

[60]  Masters,et al.  Cell line misidentification: the beginning of the end , 2010 .

[61]  Stefan Heinrichs,et al.  SNP array analysis in hematologic malignancies: avoiding false discoveries. , 2010, Blood.

[62]  Benjamin J. Raphael,et al.  Integrated Genomic Analyses of Ovarian Carcinoma , 2011, Nature.

[63]  Kathleen R. Cho,et al.  Gene expression in ovarian cancer reflects both morphology and biological behavior, distinguishing clear cell from other poor-prognosis ovarian carcinomas. , 2002, Cancer research.

[64]  A. Salgado,et al.  Failure of Y-27632 to improve the culture of adult human adipose-derived stem cells , 2015, Stem cells and cloning : advances and applications.

[65]  Wen-Lin Kuo,et al.  A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. , 2006, Cancer cell.

[66]  S. Badve,et al.  Phenotypic plasticity in normal breast derived epithelial cells , 2014, BMC Cell Biology.

[67]  Ronald W. Davis,et al.  Multiplexed genotyping with sequence-tagged molecular inversion probes , 2003, Nature Biotechnology.

[68]  R. Shoemaker The NCI60 human tumour cell line anticancer drug screen , 2006, Nature Reviews Cancer.

[69]  Hans Clevers,et al.  Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium. , 2011, Gastroenterology.

[70]  K. Coombes,et al.  A Technical Assessment of the Utility of Reverse Phase Protein Arrays for the Study of the Functional Proteome in Non-microdissected Human Breast Cancers , 2010, Clinical Proteomics.

[71]  C. Denkert,et al.  Overexpression of the plasminogen activator inhibitor type-1 in epithelial ovarian cancer. , 2006, Anticancer research.

[72]  Xuming He,et al.  Non-parametric quantification of protein lysate arrays , 2007, Bioinform..