title: Global Conservation of Protein Status between Cell Lines and Xenografts.
abstract: Common preclinical models for testing anticancer treatment include cultured human tumor cell lines in monolayer, and xenografts derived from these cell lines in immunodeficient mice. Our goal was to determine how similar the xenografts are compared with their original cell line and to determine whether it is possible to predict the stability of a xenograft model beforehand. We studied a selection of 89 protein markers of interest in 14 human cell cultures and respective subcutaneous xenografts using the reverse-phase protein array technology. We specifically focused on proteins and posttranslational modifications involved in DNA repair, PI3K pathway, apoptosis, tyrosine kinase signaling, stress, cell cycle, MAPK/ERK signaling, SAPK/JNK signaling, NFκB signaling, and adhesion/cytoskeleton. Using hierarchical clustering, most cell culture-xenograft pairs cluster together, suggesting a global conservation of protein signature. Particularly, Akt, NFkB, EGFR, and Vimentin showed very stable protein expression and phosphorylation levels highlighting that 4 of 10 pathways were highly correlated whatever the model. Other proteins were heterogeneously conserved depending on the cell line. Finally, cell line models with low Akt pathway activation and low levels of Vimentin gave rise to more reliable xenograft models. These results may be useful for the extrapolation of cell culture experiments to in vivo models in novel targeted drug discovery.
authors: Institut Curie, Centre de Recherche, 91400 Orsay/75248 Paris, France; UMR3347, Centre National de la Recherche Scientifique, 91400 Orsay, France; U1021, Institut National de la Santé et de la Recherche Médicale, 91400 Orsay, France; Université Paris Sud, 91400 Orsay, France; Clermont Auvergne University, EA7283 CREaT, 63011 Clermont-Ferrand, France; Radiotherapy Department, Centre Jean Perrin, 63011 Clermont-Ferrand, France. Electronic address: Julian.biau@clermont.unicancer.fr.
authors: Julian
authors: J
authors: Biau
authors: Clermont Auvergne University, EA7283 CREaT, 63011 Clermont-Ferrand, France; Radiotherapy Department, Centre Jean Perrin, 63011 Clermont-Ferrand, France.
authors: Emmanuel
authors: E
authors: Chautard
authors: U1103, Institut National de la Santé et de la Recherche Médicale, 63001 Clermont-Ferrand, France; UMR 6293, Centre National de la Recherche Scientifique, 63001 Clermont-Ferrand, France; Clermont Auvergne University, GReD Laboratory, Clermont-Ferrand, 63000, France.
authors: Frank
authors: F
authors: Court
authors: Biostatistics Department, DRCI, Clermont-Ferrand Hospital, Clermont-Ferrand, 63003, France.
authors: Bruno
authors: B
authors: Pereira
authors: Institut Curie, Centre de Recherche, 91400 Orsay/75248 Paris, France; UMR3347, Centre National de la Recherche Scientifique, 91400 Orsay, France; U1021, Institut National de la Santé et de la Recherche Médicale, 91400 Orsay, France; Clermont Auvergne University, EA7283 CREaT, 63011 Clermont-Ferrand, France; Radiotherapy Department, Institut Curie, 75005 Paris, France.
authors: Pierre
authors: P
authors: Verrelle
authors: Institut Curie, Centre de Recherche, 91400 Orsay/75248 Paris, France; DNA Therapeutics, Evry, Paris, France.
authors: Flavien
authors: F
authors: Devun
authors: Institut Curie, Department of Translational Research, RPPA platform,75248 Paris cedex05, France.
authors: Leanne
authors: L
authors: De Koning
authors: Institut Curie, Centre de Recherche, 91400 Orsay/75248 Paris, France; UMR3347, Centre National de la Recherche Scientifique, 91400 Orsay, France; U1021, Institut National de la Santé et de la Recherche Médicale, 91400 Orsay, France; Université Paris Sud, 91400 Orsay, France.
authors: Marie
authors: M
authors: Dutreix