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bioRxiv · 10.1101/2022.11.11.516211

Genomic variations drive phenotypic heterogeneity in pancreatic cancer cells

Xie, G.·Usman, O. H.·Kumar, S.·Patel, D.·Kavanaugh, M.·Wang, Y. J.·Irianto, J.
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Abstract

ObjectivesTo evaluate the suitability of the MIA PaCa-2 cell line for studying pancreatic cancer intratumor heterogeneity, we aim to further characterize the nature of MIA PaCa-2 cells phenotypic, genomic, and transcriptomic heterogeneity. MethodsMIA PaCa-2 single-cell clones were established through flow cytometry. For the phenotypic study, we quantified the cellular morphology, proliferation rate, migration potential, and drug sensitivity of the clones. The chromosome copy number and transcriptomic profiles were quantified using SNPa and RNA-seq, respectively. ResultsFour MIA PaCa-2 clones showed distinctive phenotypes, with differences in cellular morphology, proliferation rate, migration potential, and drug sensitivity. We also observed a degree of genomic variations between these clones in form of chromosome copy number alterations and single nucleotide variations, 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 the uniquely regulated ITGAV, which dictates the morphology of MIA PaCa-2 clones. ConclusionsMIA 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 pancreatic cancer heterogeneity.

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Xie, G., Usman, O. H., Kumar, S., Patel, D., Kavanaugh, M., Wang, Y. J., Irianto, J.. 2022-11-13. Genomic variations drive phenotypic heterogeneity in pancreatic cancer cells. https://doi.org/10.1101/2022.11.11.516211

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