BACKGROUND
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  of different clinical stages and differentiation grades or from metastatic sites originated from a colon tumor.
the major oncogenic pathways in colon cancer include loss of function mutations in apc, tp <dig> and smad <dig> , or dna mismatch repair genes, and activating mutations in beta-catenin  <cit> .
as a consequence, the wnt pathway is activated in most tumors and derived crc cell lines, albeit to a different extent, depending on the genetic lesions  <cit> .
the morphology, expression of differentiation markers, migratory characteristics and their potential to form metastases differ vastly between the cell lines  <cit> .
while cancer drug discovery has mainly focused on targeting tumor cell proliferation, the outcome of a cancer depends largely on tumor invasion and dissemination  <cit> .
recent advances in understanding underlying mechanisms in cancer biology including cancer stem cell  properties and epithelial-mesenchymal transition  and their relation to drug susceptibility require that relevant traits are considered for choosing appropriate cell-based models.
it is believed that at the invasive front, the tumor cells undergo emt resulting in increased migratory capacity.
furthermore, emt has recently been linked in breast cancer to stem cell like properties  <cit>  as well as resistance to chemotherapy in different tumor types including crc  <cit> .
the variety of available human cancer cell lines reflects the genomic heterogeneity across the human cancer population at least in part and has therefore regained attention notably to predict responsiveness of anticancer drugs  <cit> .
starting with the landmark paper by scherf et al.
<cit>  numerous studies followed that aimed at linking drug response in terms of growth inhibition with gene expression signatures, some specifically focusing on colon cancer .
to our knowledge, no study has specifically focused on linking expression of malignant traits  in colon cancer cell lines to response to therapy.
in this study we compare for the first time gene expression signatures relating to a wide panel of commonly known intestinal cell lines, primary cell cultures of human cancer-associated fibroblasts and laser-dissected human colonocytes, small intestinal enterocytes and tumor cells.
we delineate selection criteria for crc derived cell lines based on genomic expression patterns related to clinical parameters, migratory capacities and proliferative activities.
while some cell lines are mainly being used to study mechanisms associated with tumor biology others serve as models for normal enterocytes studying drug absorption.
thus, we used the same strategy to assess the validity of models for oral drug absorption.
RESULTS
most dominant gene expression differences as revealed by principal component analysis  were observed between normal epithelium and all tumor-derived cell lines, and cells with epithelial versus mesenchymal properties.
pca was performed to assess the major gene expression differences between microdissected normal and tumor epithelium, primary cancer-associated fibroblast  cultures and the various crc cell lines.
pca involves a mathematical procedure that transforms a number of possibly correlated variables into a smaller number of uncorrelated variables called principal components.
hence, the first principal component accounts for as much of the variability in the data as possible and each succeeding component accounts for as much of the remaining variability as possible.
two breast cancer cell lines with known pronounced  or weak  emt traits  <cit>  were included into the comparison.
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 cafs and epithelial cells .
t <dig>  ht <dig> and caco- <dig> cells grown to confluency for 3 weeks seemed to be most similar to the small intestinal enterocytes, and also to laser-dissected tumor cells, while sw <dig> and mb <dig> proved closest to cafs.
selection of relevant cell lines to study tumor biology based on expression of signatures related to malignant traits
next, the suitability of the various cell lines for tumor biology related studies was assessed.
there are no standard models and selection criteria are not well defined.
the activation of the wnt pathway is a hallmark in colon carcinogenesis.
recent findings indicate that the wnt activity defines crc stem cells and is regulated by the microenvironment  <cit> .
thus, the overall wnt signaling activity was compared in the various samples.
when comparing the average expression of direct wnt targets , the sw <dig> cell line showed the strongest wnt signal followed by sw <dig>  laser-dissected tumor cells, colo <dig>  dld <dig> and undifferentiated caco- <dig> cells .
the ranking of cell lines with strong, medium and low average expression of direct wnt targets was in agreement with the wnt activity based on topflash assays reported by rosin-arbesfeld and co-workers  <cit> .
moreover, the expression of genes involved in emt  and a set of genes, recently being described as “humanized intestinal stem cell signature” , which identified recurrent crc  <cit> , were studied to rank the cell lines as models for tumor cells at the invasive front and/or tumor cells with stemness characteristics.
survival analysis studies showed that risk of recurrence was significantly higher for crc patients with a strong emt signature and also correlated with overall survival .
as expected cafs and mb <dig>  had the strongest expression of the emt signature followed by colo <dig>  sw <dig>  sw <dig> and laser-dissected tumor epithelial cells, normal colonocytes and differentiated caco- <dig> cells.
though colo <dig> cells ranked highest of all intestinal epithelial cells, they also had the highest expression of cdx <dig>  a key player in the maturation of intestinal enterocytes  <cit> .
when the cell lines were ranked to the overall expression of stem cell related genes , the five top ranked samples were caf > mb231 > laser-dissected tumor cells > sw480 > lovo .
in summary, with respect to the wnt, emt and huisc signatures, sw <dig> proved the cell line with the strongest traits and a gene expression pattern most similar to that of micro-dissected tumor epithelium.
emt = emt-related genes, huisc=“humanized intestinal stem cell signature”, wnt = direct wnt targets, trans_bc = transporters known to play important role in oral drug absorption, slc_si3 = solute carriers expressed at a significantly higher level in small intestinal samples versus colon samples, slc_pm = solute carriers of the plasma membrane, abc = abc transporters, mki67_co: set of genes correlating with mki <dig> expression in colon cancer samples, ic50_pos, ic50_neg: genes with either strong positive or negative correlation between gi <dig> values of chemotherapeutics and expression across  <dig> cell line panel .
tumor = laser dissected tumor cells, normal = laser dissected colonocytes, je, il = laser dissected enterocytes of the jejunum or ileum, respectively, d = differentiated, u = undifferentiated, fi = grown on filters, fl = grown in flasks, r = resistant to methotraxate, s = sensitive to methotrexate.
gain of malignant traits and loss of differentiation signature were associated with migratory properties
invasive tumor cells acquire higher motility through emt  <cit> .
thus, we elucidated to what extent genomic expression characteristics could be linked to migratory properties.
in general, the analysis revealed that higher migratory propensity was associated with strong emt traits and weak expression of a signature derived from normal small intestinal epithelium .
accordingly, sw <dig> and mb <dig> cells showed the highest migratory capacity .
transporter profile defines absorption model
the model of choice to evaluate drug absorption are caco- <dig> cells as they undergo in vitro spontaneous enterocytic differentiation by developing an apical brush border membrane endowed with hydrolases such as sucrase-isomaltase and aminopeptidase n  <cit> .
on the other hand, comparison of permeability coefficients across different laboratories is still an issue  <cit> .
various studies have compared the genomic profiles of caco- <dig> cells to large and small intestinal tissue  <cit> .
none of these has systematically compared these profiles to the ones of small intestinal enterocytes in comparison to other intestinal cell lines, and, in particular, to profiles of the genes relevant for active transport.
consequently, we made use of our objective approach to assess the suitability of the caco- <dig> cells as model for oral drug absorption as compared to other crc derived cell lines, taking inter-laboratory differences into account.
as described above, pca suggested that t <dig>  ht <dig> and caco- <dig> cells grown to confluency for 3 weeks were most similar to small intestinal enterocytes.
yet, when performing pca filtering on solute carriers, transporters mostly responsible for active uptake, differentiated caco- <dig> cells emerged as most akin to small intestinal enterocytes .
when the analysis was extended to include expression of drug transporters known to be involved in uptake and secretion in the small intestine , differentiated caco- <dig> cells clustered with normal colonocytes as well as small intestinal enterocytes .
however, when focusing only on transporters potentially relevant for uptake , differentiated caco- <dig> cells clustered only with small intestinal enterocytes .
when focusing on abc transporters, differentiated caco- <dig> cells clustered with ht <dig> and t <dig> cells , suggesting that these cell lines could also serve as a model for active export.
focusing on the expression of slcs specific for the small intestine , differentiated caco- <dig> cells, however, ranked highest independent of culture conditions and origins .
selection criteria for chemo-sensitivity studies
recent reports suggest that chemotherapy may lead to a selection of tumor cells with emt and stem cell properties and increased chemo-resistance  <cit> .
for example, gupta et al.
<cit>  suggested that treatment with paclitaxel as compared to salinomycin significantly enriched breast cancer cells with emt properties.
thus, we examined their data set  and found that our emt signature was also significantly enriched when performing gsea .
using the same approach, however, we could not observe any significant enrichment  of this emt signature in either oxaliplatin-treated ht <dig>  dld <dig> and lovo cells , or methotrexate-treated ht <dig> and caco- <dig> cells  as compared to untreated cells.
of note, however, that the stem cell signature huisc was enriched in methotrexate treated caco- <dig> cells .
to extend this analysis we addressed more comprehensively to what extent emt, huisc and wnt signatures correlated with gi <dig> values of  <dig> commonly used chemotherapeutics in the nci <dig> cell line panel .
unexpectedly, no correlation between expression of emt, huisc and wnt signatures and gi <dig> values was observed , and furthermore, rank orders in terms of emt, huisc and wnt signatures of  <dig> crc cell lines comprised within the nci <dig> panel  did not reveal any positive correlation with gi <dig> values, yet even a tendency to a negative link .
most chemotherapeutics interfere with the cell cycle activities and accordingly cell proliferation has been associated with susceptibility to chemotherapy  <cit> .
as expected, a positive correlation between expression of proliferation associated genes and gi <dig> values was observed across the nci <dig> cell lines .
the crc cell lines tested herein  displayed no significant difference in proliferation  and no link was observed between their rank orders  and gi <dig> values .
finally, we scrutinized the nci <dig> data sets for genes whose expression was either positively or negatively correlated with gi <dig> values of chemotherapeutics .
clustering of the correlation coefficients revealed two distinct gene sets  for which the median positive and negative correlation coefficients were determined .
interestingly, a link could be observed between rank orders of the crc cell lines  and gi <dig> values , suggesting that these new signatures might be worth pursuing for assessing chemo-sensitivity.
discussion
selection criteria for cell-based models are often ill defined and arbitrary.
here we propose to make use of publicly available data generated by high throughput technologies to guide the choice of cell lines according to more objective criteria, such as gene expression signatures for selected traits.
focusing on crc cell lines, we validated this approach for three different fields of application, i.e.
the identification of cell lines most relevant for modeling and investigating tumor cell invasion, drug absorption and/or transport, and response to chemotherapy.
though we have focused on specific selection criteria, our strategy may be applied to any type of selection criteria .
models to study tumor biology
in view of the heterogeneity of solid tumors  <cit>  and the challenge to identify adequate cell-based models, we assessed to what extent comparative data mining for identifying tumor traits that overlap in tumor samples and cell lines might contribute to improving the relevance of cell-based models.
we therefore ranked a panel of crc cell lines using emt and huisc signatures to assess to what extent such signatures reflect invasive tumor behavior.
reports on in vivo studies with these cell lines indeed validate our ranking criteria.
thus, sw <dig>  sw <dig>  colo <dig> and hct <dig> cells, which all ranked high in our assessment for emt and huisc signatures, showed the highest propensity for local invasion upon orthotopic grafting  <cit> , whereas ht <dig>  colo <dig> and dld <dig>  which ranked lower for these traits, showed less aggressive behavior.
de vries and co-workers observed that sw <dig> cells were indeed strongly invasive in vitro, in vivo, however, they proved less invasive than ht <dig> and ls174t cells  <cit> .
collectively, unbiased data mining allowed identifying cell lines with prominent mesenchymal traits , which display migratory properties and represent an invasive phenotype, whereas ht <dig>  the most frequently used crc model line, and t <dig> cells, which both ranked low for these traits came closest to gene expression profiles of bulk tumor tissue cells .
caco- <dig> cells, a model of choice for drug absorption
screening the literature with key words such as “absorption” and “transporters” revealed that, within the crc cell line panel assessed herein, caco- <dig> is the most widely used intestinal cell line for absorption-related studies  <cit> .
comparing transporter gene expression profiles revealed that differentiated caco- <dig> cells indeed most accurately recapitulate those of normal enterocytes.
similar to hayeshi et al.
<cit> , we observed that culture conditions influence the expression pattern of selected transporters.
based on our ranking method we show that caco- <dig> cells grown for three weeks, independently of their origin and culture conditions, best match the genomic profiles of small intestinal enterocytes.
chemo-sensitivity
selection of tumor cells with emt and stem cell properties and higher chemo-resistance has recently emerged as a novel mechanism underlying therapy-resistance  <cit> .
vast databases with gi <dig> values, a standard to assess drug sensitivity  <cit> , are available for the intestinal crc lines ht <dig>  colo <dig>  km <dig>  sw <dig>  hct <dig>  hcc_ <dig> and hct <dig> through the nci database .
we therefore probed these data sets for a correlation between emt and csc signatures and chemoresistance.
using the emt signature defined herein, we could indeed confirm such a correlation in the breast cancer data set of gupta et al.
<cit> .
however, we could not observe any significant association of emt-related genes with the gi <dig> values of crc cell lines .
interestingly, novel chemoresistance-associated signatures could be identified; indicating that in crc cell lines expression of emt and csc signatures are not dominant factors in the response to therapy.
cell line- or treatment-specific effects may account for this discrepancy.
it is of note that gupta and co-authors compared paclitaxel vs. salinomycin-treated cells, while the other data were based on treatment versus non-treatment comparisons.
a correlation between drug resistance and emt features has, however, been observed using crc biopsies  <cit> .
as these may contain variable amounts of stroma and as stroma content may influence response to therapy  <cit> , these data are not directly comparable to gi <dig> values of crc cell lines.
CONCLUSIONS
we have presented 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.
in summary, we conclude that sw <dig> 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, therefore a good model to study invasive tumor cells.
on the other hand, differentiated ht <dig> and t <dig> cells showed gene expression patterns closest to tumor bulk derived cells.
regarding drug absorption, we confirmed that differentiated caco- <dig> cells are the model of choice for active uptake studies in the small intestine.

 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 of different clinical stages and differentiation grades or from metastatic sites originated from a colon tumor. the major oncogenic pathways in colon cancer include loss of function mutations in apc, tp and smad, or dna mismatch repair genes, and activating mutations in beta-catenin. as a consequence, the wnt pathway is activated in most tumors and derived crc cell lines, albeit to a different extent, depending on the genetic lesions. the morphology, expression of differentiation markers, migratory characteristics and their potential to form metastases differ vastly between the cell lines. while cancer drug discovery has mainly focused on targeting tumor cell proliferation, the outcome of a cancer depends largely on tumor invasion and dissemination. recent advances in understanding underlying mechanisms in cancer biology including cancer stem cell properties and epithelial-mesenchymal transition and their relation to drug susceptibility require that relevant traits are considered for choosing appropriate cell-based models. it is believed that at the invasive front, the tumor cells undergo emt resulting in increased migratory capacity. furthermore, emt has recently been linked in breast cancer to stem cell like properties as well as resistance to chemotherapy in different tumor types including crc. the variety of available human cancer cell lines reflects the genomic heterogeneity across the human cancer population at least in part and has therefore regained attention notably to predict responsiveness of anticancer drugs. starting with the landmark paper by scherf et al. numerous studies followed that aimed at linking drug response in terms of growth inhibition with gene expression signatures, some specifically focusing on colon cancer. to our knowledge, no study has specifically focused on linking expression of malignant traits in colon cancer cell lines to response to therapy. in this study we compare for the first time gene expression signatures relating to a wide panel of commonly known intestinal cell lines, primary cell cultures of human cancer-associated fibroblasts and laser-dissected human colonocytes, small intestinal enterocytes and tumor cells. we delineate selection criteria for crc derived cell lines based on genomic expression patterns related to clinical parameters, migratory capacities and proliferative activities. while some cell lines are mainly being used to study mechanisms associated with tumor biology others serve as models for normal enterocytes studying drug absorption. thus, we used the same strategy to assess the validity of models for oral drug absorption.  most dominant gene expression differences as revealed by principal component analysis were observed between normal epithelium and all tumor-derived cell lines, and cells with epithelial versus mesenchymal properties. pca was performed to assess the major gene expression differences between microdissected normal and tumor epithelium, primary cancer-associated fibroblast cultures and the various crc cell lines. pca involves a mathematical procedure that transforms a number of possibly correlated variables into a smaller number of uncorrelated variables called principal components. hence, the first principal component accounts for as much of the variability in the data as possible and each succeeding component accounts for as much of the remaining variability as possible. two breast cancer cell lines with known pronounced or weak emt traits were included into the comparison. 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 cafs and epithelial cells. t ht and caco- cells grown to confluency for 3 weeks seemed to be most similar to the small intestinal enterocytes, and also to laser-dissected tumor cells, while sw and mb proved closest to cafs. selection of relevant cell lines to study tumor biology based on expression of signatures related to malignant traits next, the suitability of the various cell lines for tumor biology related studies was assessed. there are no standard models and selection criteria are not well defined. the activation of the wnt pathway is a hallmark in colon carcinogenesis. recent findings indicate that the wnt activity defines crc stem cells and is regulated by the microenvironment. thus, the overall wnt signaling activity was compared in the various samples. when comparing the average expression of direct wnt targets, the sw cell line showed the strongest wnt signal followed by sw laser-dissected tumor cells, colo dld and undifferentiated caco- cells. the ranking of cell lines with strong, medium and low average expression of direct wnt targets was in agreement with the wnt activity based on topflash assays reported by rosin-arbesfeld and co-workers. moreover, the expression of genes involved in emt and a set of genes, recently being described as “humanized intestinal stem cell signature”, which identified recurrent crc, were studied to rank the cell lines as models for tumor cells at the invasive front and/or tumor cells with stemness characteristics. survival analysis studies showed that risk of recurrence was significantly higher for crc patients with a strong emt signature and also correlated with overall survival. as expected cafs and mb had the strongest expression of the emt signature followed by colo sw sw and laser-dissected tumor epithelial cells, normal colonocytes and differentiated caco- cells. though colo cells ranked highest of all intestinal epithelial cells, they also had the highest expression of cdx a key player in the maturation of intestinal enterocytes. when the cell lines were ranked to the overall expression of stem cell related genes, the five top ranked samples were caf > mb231 > laser-dissected tumor cells > sw480 > lovo. in summary, with respect to the wnt, emt and huisc signatures, sw proved the cell line with the strongest traits and a gene expression pattern most similar to that of micro-dissected tumor epithelium. emt = emt-related genes, huisc=“humanized intestinal stem cell signature”, wnt = direct wnt targets, trans_bc = transporters known to play important role in oral drug absorption, slc_si3 = solute carriers expressed at a significantly higher level in small intestinal samples versus colon samples, slc_pm = solute carriers of the plasma membrane, abc = abc transporters, mki67_co: set of genes correlating with mki expression in colon cancer samples, ic50_pos, ic50_neg: genes with either strong positive or negative correlation between gi values of chemotherapeutics and expression across cell line panel. tumor = laser dissected tumor cells, normal = laser dissected colonocytes, je, il = laser dissected enterocytes of the jejunum or ileum, respectively, d = differentiated, u = undifferentiated, fi = grown on filters, fl = grown in flasks, r = resistant to methotraxate, s = sensitive to methotrexate. gain of malignant traits and loss of differentiation signature were associated with migratory properties invasive tumor cells acquire higher motility through emt. thus, we elucidated to what extent genomic expression characteristics could be linked to migratory properties. in general, the analysis revealed that higher migratory propensity was associated with strong emt traits and weak expression of a signature derived from normal small intestinal epithelium. accordingly, sw and mb cells showed the highest migratory capacity. transporter profile defines absorption model the model of choice to evaluate drug absorption are caco- cells as they undergo in vitro spontaneous enterocytic differentiation by developing an apical brush border membrane endowed with hydrolases such as sucrase-isomaltase and aminopeptidase n. on the other hand, comparison of permeability coefficients across different laboratories is still an issue. various studies have compared the genomic profiles of caco- cells to large and small intestinal tissue. none of these has systematically compared these profiles to the ones of small intestinal enterocytes in comparison to other intestinal cell lines, and, in particular, to profiles of the genes relevant for active transport. consequently, we made use of our objective approach to assess the suitability of the caco- cells as model for oral drug absorption as compared to other crc derived cell lines, taking inter-laboratory differences into account. as described above, pca suggested that t ht and caco- cells grown to confluency for 3 weeks were most similar to small intestinal enterocytes. yet, when performing pca filtering on solute carriers, transporters mostly responsible for active uptake, differentiated caco- cells emerged as most akin to small intestinal enterocytes. when the analysis was extended to include expression of drug transporters known to be involved in uptake and secretion in the small intestine, differentiated caco- cells clustered with normal colonocytes as well as small intestinal enterocytes. however, when focusing only on transporters potentially relevant for uptake, differentiated caco- cells clustered only with small intestinal enterocytes. when focusing on abc transporters, differentiated caco- cells clustered with ht and t cells, suggesting that these cell lines could also serve as a model for active export. focusing on the expression of slcs specific for the small intestine, differentiated caco- cells, however, ranked highest independent of culture conditions and origins. selection criteria for chemo-sensitivity studies recent reports suggest that chemotherapy may lead to a selection of tumor cells with emt and stem cell properties and increased chemo-resistance. for example, gupta et al. suggested that treatment with paclitaxel as compared to salinomycin significantly enriched breast cancer cells with emt properties. thus, we examined their data set and found that our emt signature was also significantly enriched when performing gsea. using the same approach, however, we could not observe any significant enrichment of this emt signature in either oxaliplatin-treated ht dld and lovo cells, or methotrexate-treated ht and caco- cells as compared to untreated cells. of note, however, that the stem cell signature huisc was enriched in methotrexate treated caco- cells. to extend this analysis we addressed more comprehensively to what extent emt, huisc and wnt signatures correlated with gi values of commonly used chemotherapeutics in the nci cell line panel. unexpectedly, no correlation between expression of emt, huisc and wnt signatures and gi values was observed, and furthermore, rank orders in terms of emt, huisc and wnt signatures of crc cell lines comprised within the nci panel did not reveal any positive correlation with gi values, yet even a tendency to a negative link. most chemotherapeutics interfere with the cell cycle activities and accordingly cell proliferation has been associated with susceptibility to chemotherapy. as expected, a positive correlation between expression of proliferation associated genes and gi values was observed across the nci cell lines. the crc cell lines tested herein displayed no significant difference in proliferation and no link was observed between their rank orders and gi values. finally, we scrutinized the nci data sets for genes whose expression was either positively or negatively correlated with gi values of chemotherapeutics. clustering of the correlation coefficients revealed two distinct gene sets for which the median positive and negative correlation coefficients were determined. interestingly, a link could be observed between rank orders of the crc cell lines and gi values, suggesting that these new signatures might be worth pursuing for assessing chemo-sensitivity. discussion selection criteria for cell-based models are often ill defined and arbitrary. here we propose to make use of publicly available data generated by high throughput technologies to guide the choice of cell lines according to more objective criteria, such as gene expression signatures for selected traits. focusing on crc cell lines, we validated this approach for three different fields of application, i.e. the identification of cell lines most relevant for modeling and investigating tumor cell invasion, drug absorption and/or transport, and response to chemotherapy. though we have focused on specific selection criteria, our strategy may be applied to any type of selection criteria. models to study tumor biology in view of the heterogeneity of solid tumors and the challenge to identify adequate cell-based models, we assessed to what extent comparative data mining for identifying tumor traits that overlap in tumor samples and cell lines might contribute to improving the relevance of cell-based models. we therefore ranked a panel of crc cell lines using emt and huisc signatures to assess to what extent such signatures reflect invasive tumor behavior. reports on in vivo studies with these cell lines indeed validate our ranking criteria. thus, sw sw colo and hct cells, which all ranked high in our assessment for emt and huisc signatures, showed the highest propensity for local invasion upon orthotopic grafting, whereas ht colo and dld which ranked lower for these traits, showed less aggressive behavior. de vries and co-workers observed that sw cells were indeed strongly invasive in vitro, in vivo, however, they proved less invasive than ht and ls174t cells. collectively, unbiased data mining allowed identifying cell lines with prominent mesenchymal traits, which display migratory properties and represent an invasive phenotype, whereas ht the most frequently used crc model line, and t cells, which both ranked low for these traits came closest to gene expression profiles of bulk tumor tissue cells. caco- cells, a model of choice for drug absorption screening the literature with key words such as “absorption” and “transporters” revealed that, within the crc cell line panel assessed herein, caco- is the most widely used intestinal cell line for absorption-related studies. comparing transporter gene expression profiles revealed that differentiated caco- cells indeed most accurately recapitulate those of normal enterocytes. similar to hayeshi et al., we observed that culture conditions influence the expression pattern of selected transporters. based on our ranking method we show that caco- cells grown for three weeks, independently of their origin and culture conditions, best match the genomic profiles of small intestinal enterocytes. chemo-sensitivity selection of tumor cells with emt and stem cell properties and higher chemo-resistance has recently emerged as a novel mechanism underlying therapy-resistance. vast databases with gi values, a standard to assess drug sensitivity, are available for the intestinal crc lines ht colo km sw hct hcc_ and hct through the nci database. we therefore probed these data sets for a correlation between emt and csc signatures and chemoresistance. using the emt signature defined herein, we could indeed confirm such a correlation in the breast cancer data set of gupta et al.. however, we could not observe any significant association of emt-related genes with the gi values of crc cell lines. interestingly, novel chemoresistance-associated signatures could be identified; indicating that in crc cell lines expression of emt and csc signatures are not dominant factors in the response to therapy. cell line- or treatment-specific effects may account for this discrepancy. it is of note that gupta and co-authors compared paclitaxel vs. salinomycin-treated cells, while the other data were based on treatment versus non-treatment comparisons. a correlation between drug resistance and emt features has, however, been observed using crc biopsies. as these may contain variable amounts of stroma and as stroma content may influence response to therapy, these data are not directly comparable to gi values of crc cell lines.  we have presented 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. in summary, we conclude that sw 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, therefore a good model to study invasive tumor cells. on the other hand, differentiated ht and t cells showed gene expression patterns closest to tumor bulk derived cells. regarding drug absorption, we confirmed that differentiated caco- cells are the model of choice for active uptake studies in the small intestine. 
this study presents a straightforward strategy to exploit publicly available gene expression data to guide the choice of cell-based models. 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. 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. on the other hand, differentiated ht and t cells showed gene expression patterns closest to tumor bulk derived cells. regarding drug absorption, we confirmed that differentiated caco- cells are the model of choice for active uptake studies in the small intestine. 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 and stemness, migratory properties, proliferative activity, transporter expression profiles and chemosensitivity. cell linesgenomic profilingmalignant traitsepithelial-mesenchymal transitionintestinecolon cancerchemosensitivity however, a novel signature was identified through mining of nci gi values that allowed to rank the panel of intestinal cell lines according to their drug responsiveness to commonly used chemotherapeutics. for example, sw 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. 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 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 and stemness, migratory properties, proliferative activity, transporter expression profiles and chemosensitivity. for example, sw 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 ht and t cells showed gene expression patterns closest to tumor bulk derived cells. regarding drug absorption, we confirmed that differentiated caco- 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 nci gi 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. cell linesgenomic profilingmalignant traitsepithelial-mesenchymal transitionintestinecolon cancerchemosensitivity 