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Open Access Research article

Defining new criteria for selection of cell-based intestinal models using publicly available databases

Jon Christensen1, Sara El-Gebali2, Manuela Natoli3, Thierry Sengstag4, Mauro Delorenzi56, Susanne Bentz27, Hanifa Bouzourene8, Martin Rumbo9, Armando Felsani3, Sanna Siissalo10, Jouni Hirvonen10, Maya R Vila11, Piercarlo Saletti12, Michel Aguet136 and Pascale Anderle142567*

Author affiliations

1 Institute for Macromolecular Chemistry and Center for Biological Signaling Studies (BIOSS), University of Freiburg, Freiburg, Germany

2 Institute of Biochemistry and Molecular Medicine, University of Berne, Berne, Switzerland

3 Istituto di Biologia Cellulare e Neurobiologia, CNR, Rome, Italy

4 OSC - Omics Science Center, RIKEN Yokohama Institute, Yokohama, Japan

5 Swiss Institute of Bioinformatics, Lausanne, Switzerland

6 Swiss National Centre of Competence in Research Molecular Oncology, Swiss Institute for Experimental Cancer Research, Ecole Polytechnique Fédérale de Lausanne, School of Life Sciences, Lausanne, Switzerland

7 NCCR TransCure, University of Berne, Berne, Switzerland

8 Institute of pathology of Lausanne, Centre hospitalier et universitaire vaudois, Lausanne, Switzerland

9 Laboratorio de Investigaciones del Sistema Inmune (LISIN), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina

10 Faculty of Pharmacy, University of Helsinki, Helsinki, Finland

11 LEITAT Technological Center, Barcelona, Spain

12 Medical Oncology Department, IOSI, Ospedale Regionale di Lugano, Lugano, Switzerland

13 Swiss Institute for Experimental Cancer Research, Ecole Polytechnique Fédérale de Lausanne, School of Life Sciences, Lausanne, Switzerland

14 Institute of Biochemistry and Molecular Medicine, University of Bern, Buehlstrasse 28, 3000, Bern 9, Switzerland

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Citation and License

BMC Genomics 2012, 13:274  doi:10.1186/1471-2164-13-274

Published: 22 June 2012

Abstract

Background

The criteria for choosing relevant cell lines among a vast panel of available intestinal-derived lines exhibiting a wide range of functional properties are still ill-defined. The objective of this study was, therefore, to establish objective criteria for choosing relevant cell lines to assess their appropriateness as tumor models as well as for drug absorption studies.

Results

We made use of publicly available expression signatures and cell based functional assays to delineate differences between various intestinal colon carcinoma cell lines and normal intestinal epithelium. We have compared a panel of intestinal cell lines with patient-derived normal and tumor epithelium and classified them according to traits relating to oncogenic pathway activity, epithelial-mesenchymal transition (EMT) and stemness, migratory properties, proliferative activity, transporter expression profiles and chemosensitivity. For example, SW480 represent an EMT-high, migratory phenotype and scored highest in terms of signatures associated to worse overall survival and higher risk of recurrence based on patient derived databases. On the other hand, differentiated HT29 and T84 cells showed gene expression patterns closest to tumor bulk derived cells. Regarding drug absorption, we confirmed that differentiated Caco-2 cells are the model of choice for active uptake studies in the small intestine. Regarding chemosensitivity we were unable to confirm a recently proposed association of chemo-resistance with EMT traits. However, a novel signature was identified through mining of NCI60 GI50 values that allowed to rank the panel of intestinal cell lines according to their drug responsiveness to commonly used chemotherapeutics.

Conclusions

This study presents a straightforward strategy to exploit publicly available gene expression data to guide the choice of cell-based models. While this approach does not overcome the major limitations of such models, introducing a rank order of selected features may allow selecting model cell lines that are more adapted and pertinent to the addressed biological question.

Keywords:
Cell lines; Genomic profiling; Malignant traits; Epithelial-mesenchymal transition; Intestine; Colon cancer; Chemosensitivity