Abstract
BackgroundThe 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.ResultsWe 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.ConclusionsThis 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.
Highlights
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
All of these cell lines are either directly derived from primary colo-rectal cancers (CRCs) of different clinical stages and differentiation grades or from metastatic sites originated from a colon tumor
The first component was defined mainly by the difference between small intestinal enterocytes and all CRC cell lines grown to subconfluency, while the second component was delineated by the difference between cancer-associated fibroblast (CAF) and epithelial cells (Figure 1)
Summary
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. A wide panel of intestinal cell lines is being used to study the biology of the intestine All of these cell lines are either directly derived from primary colo-rectal cancers (CRCs) of different clinical stages and differentiation grades or from metastatic sites originated from a colon tumor. Recent advances in understanding underlying mechanisms in cancer biology including cancer stem cell (CSC) properties and epithelial-mesenchymal transition (EMT) and their relation to drug susceptibility require that relevant traits are considered for choosing appropriate cell-based models. EMT has recently been linked in breast cancer to stem cell like properties [10] as well as resistance to chemotherapy in different tumor types including CRC [11,12,13,14]
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