Phenotypic, genomic, and transcriptomic heterogeneity in a pancreatic cancer cell line

Abstract

AbstractIntratumor phenotypic, genomic, and transcriptomic heterogeneity in pancreatic cancer have been reported by multiple studies; however, little is known about the heterogeneity’s underlying mechanisms. One possible approach to studying this is to perform a mechanistic study using pancreatic ductal adenocarcinoma (PDAC) cancer cell lines that show such heterogeneity. Here, to evaluate the suitability of the MIA PaCa-2 cell line for studying heterogeneity, we further characterize the nature of MIA PaCa-2 cells’ phenotypic, genomic, and transcriptomic heterogeneity. Four MIA PaCa-2 clones showed distinctive phenotypes, with differences in cellular morphology, proliferation rate, and migration potential. We also observed a degree of genomic variations between these clones in form of chromosome copy number alterations, suggesting the genomic heterogeneity of the population, and the intrinsic genomic instability of MIA PaCa-2 cells. Lastly, transcriptomic analysis of the clones also revealed gene expression profile differences between the clones, including uniquely regulatedITGAV, which dictates the morphology of MIA PaCa-2 clones. In conclusion, our study showed that MIA PaCa-2 is comprised of cells with distinctive phenotypes, heterogeneous genomes, and differential transcriptomic profiles, suggesting its suitability as a model to study the underlying mechanisms behind PDAC tumor phenotypic, genomic, and transcriptomic heterogeneity.