An engineered pancreatic cancer model with intra-tumoral heterogeneity of driver mutations

Moon, Hye-ran
Ozcelikkale, Altug
Yang, Yi
Elzey, Bennett D.
Konieczny, Stephen F.
Han, Bumsoo
Pancreatic ductal adenocarcinoma (PDAC) is a complex disease with significant intra-tumoral heterogeneity (ITH). Currently, no reliable PDAC tumor model is available that can present ITH profiles in a controlled manner. We develop an in vitro microfluidic tumor model mimicking the heterogeneous accumulation of key driver mutations of human PDAC using cancer cells derived from genetically engineered mouse models. These murine pancreatic cancer cell lines have KPC (Kras and Trp53 mutations) and KIC genotypes (Kras mutation and Cdkn2a deletion). Also, the KIC genotypes have two distinct phenotypes - mesenchymal or epithelial. The tumor model mimics the ITH of human PDAC to study the effects of ITH on the gemcitabine response. The results show gemcitabine resistance induced by ITH. Remarkably, it shows that cancer cell-cell interactions induce the gemcitabine resistance potentially through epithelial-mesenchymal-transition. The tumor model can provide a useful testbed to study interaction mechanisms between heterogeneous cancer cell subpopulations.


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Biomarkers may facilitate detection of gastric cancer at an earlier stage and reduce mortality. Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). Serum IgG was released and analyzed using nano-LC–TOF mass spectrometry. Statistically significant false discovery rate (FDR)-adjusted p-values were observed for 18 glycans, eight that differed significantly between NAG ...
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The inhibition of the caspase-3 enzyme is reported to increase neuronal cell survival following cerebral ischemia. The peptide Z-DEVD-FMK is a specific caspase inhibitor, which significantly reduces vulnerability to the neuronal cell death. However, this molecule is unable to cross the blood-brain barrier (BBB) and to diffuse into the brain tissue. Thus, the development of an effective delivery system is needed to provide sufficient drug concentration into the brain to prevent cell death. Using the avidin (...
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G-quadruplex secondary structures have gained significant recognition due to the discovery of their involvement in regulation of gene expression and their association with many diseases such as cancer and neurological disorders. Consequently, the need for the recognition and characterization of G-quadruplex structures has increased considerably. Here, we present a rapid, facile and sensitive off-on-off in vitro platform for G-quadruplex detection, based on the gold nanoparticle-azacyanine5 (AuNP-Aza5) conju...
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Freezing of biomaterials is important in a wide variety of biomedical applications, including cryopreservation and cryosurgeries. For the success of these applications to various biomaterials, biophysical mechanisms, which determine freezing-induced changes in cells and tissues, need to be well understood. Specifically, the significance of the intracellular mechanics during freezing is not well understood. Thus, we hypothesize that cells interact during freezing with the surroundings such as suspension medi...
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One of the molecular mechanisms underlying the plant–pathogen interactions is the regulation of gene expressions in plant responses by microRNAs which are either stimulated or silenced against pathogen attacks. Among the plant miRNAs, we found that mir159 is one of which that differentially expressed upon Blumeria graminis f. sp. hordei (Bgh) infected resistant and susceptible barley lines. The study aims to confirm its role in regulating one of its putative target genes, GaMyb transcription factor, in vivo...
Citation Formats
H.-r. Moon, A. Ozcelikkale, Y. Yang, B. D. Elzey, S. F. Konieczny, and B. Han, “An engineered pancreatic cancer model with intra-tumoral heterogeneity of driver mutations,” LAB ON A CHIP, pp. 3720–3732, 2020, Accessed: 00, 2020. [Online]. Available: