Defining new criteria for selection of cell-based intestinal models using publicly available databases
- Equal contributors
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
BMC Genomics 2012, 13:274 doi:10.1186/1471-2164-13-274Published: 22 June 2012
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.
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.
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.