Defining new criteria for selection of cell-based intestinal models using publicly available databases.
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.
1Institute for Macromolecular Chemistry and Center for Biological Signaling Studies (BIOSS), University of Freiburg, Freiburg, Germany.
Jon
J
Christensen
Sara
S
El-Gebali
Manuela
M
Natoli
Thierry
T
Sengstag
Mauro
M
Delorenzi
Susanne
S
Bentz
Hanifa
H
Bouzourene
Martin
M
Rumbo
Armando
A
Felsani
Sanna
S
Siissalo
Jouni
J
Hirvonen
Maya R
MR
Vila
Piercarlo
P
Saletti
Michel
M
Aguet
Pascale
P
Anderle
D000970:Antineoplastic Agents / Q000494:pharmacology; D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism; D030541:Databases, Genetic; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D008954:Models, Biological; D025341:Principal Component Analysis
D000970:Antineoplastic Agents