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

Autor: Hanifa Bouzourene, Pascale Anderle, Mauro Delorenzi, Sanna Siissalo, Susanne Bentz, Jon Christensen, Armando Felsani, Manuela Natoli, Thierry Sengstag, Michel Aguet, Piercarlo Saletti, Martín Rumbo, Maya R Vila, Jouni Hirvonen, Sara El-Gebali
Přispěvatelé: Faculty of Pharmacy, Division of Pharmaceutical Technology (-2019), Division of Pharmaceutical Chemistry and Technology
Jazyk: angličtina
Předmět:
Antineoplastic Agents/pharmacology
Caco-2 Cells
Cell Differentiation/drug effects
Cell Line
Tumor
Colonic Neoplasms/genetics
Colonic Neoplasms/metabolism
Databases
Genetic
Drug Resistance
Neoplasm
Epithelial-Mesenchymal Transition/drug effects
Gene Expression Regulation
Neoplastic
HT29 Cells
Humans
Intestinal Mucosa/cytology
Intestinal Mucosa/metabolism
Models
Biological
Principal Component Analysis
Cellular differentiation
Cell
Malignant traits
CARCINOMA-CELLS
COLON CANCER
MESENCHYMAL TRANSITIONS
computer.software_genre
COLORECTAL-CANCER
purl.org/becyt/ford/1 [https]
0302 clinical medicine
Intestinal mucosa
CHEMOSENSITIVITY
INTESTINE
genetics
Intestinal Mucosa
GENE-EXPRESSION
Regulation of gene expression
0303 health sciences
Database
Cell Differentiation
EPITHELIAL-CELLS
MALIGNANT TRAITS
Bioquímica y Biología Molecular
Epithelial-mesenchymal transition
Phenotype
EPITHELIAL-MESENCHYMAL TRANSITION
Intestine
Colon cancer
CELL LINES
medicine.anatomical_structure
317 Pharmacy
030220 oncology & carcinogenesis
Colonic Neoplasms
Cell lines
ANTICANCER AGENTS
DNA microarray
Stem cell
STEM-CELLS
CIENCIAS NATURALES Y EXACTAS
Research Article
Biotechnology
COLON-CANCER CELLS
lcsh:QH426-470
phenotype
lcsh:Biotechnology
education
GENOMIC PROFILING
Antineoplastic Agents
Biology
Ciencias Biológicas
03 medical and health sciences
lcsh:TP248.13-248.65
medicine
Genetics
BREAST-CANCER
purl.org/becyt/ford/1.6 [https]
protein expression
Chemosensitivity
Ciencias Exactas
030304 developmental biology
Genomic profiling
intestine epithelium cell
lcsh:Genetics
cytology
CACO-2 CELLS
computer
metabolism
Zdroj: CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET
BMC Genomics, vol. 13, pp. 274
BMC Genomics
SEDICI (UNLP)
Universidad Nacional de La Plata
instacron:UNLP
BMC Genomics, Vol 13, Iss 1, p 274 (2012)
Christensen, Jon; El-Gebali, Sara; Natoli, Manuela; Sengstag, Thierry; Delorenzi, Mauro; Bentz, Susanne; Bouzourene, Hanifa; Rumbo, Martin; Felsani, Armando; Siissalo, Sanna; Hirvonen, Jouni; Vila, Maya R; Saletti, Piercarlo; Aguet, Michel; Anderle, Pascale (2012). Defining new criteria for selection of cell-based intestinal models using publicly available databases. BMC Genomics, 13, p. 274. London: BioMed Central 10.1186/1471-2164-13-274
ISSN: 1471-2164
DOI: 10.1186/1471-2164-13-274
Popis: 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.
Facultad de Ciencias Exactas
Databáze: OpenAIRE
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