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Electrophysiology-based stratification of pancreatic tumorigenicity by label-free single-cell impedance cytometry
- Source :
- Anal Chim Acta
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer lacking specific biomarkers that can be correlated to disease onset, promotion and progression. To assess whether tumor cell electrophysiology may serve as a marker for PDAC tumorigenicity, we use multi-frequency impedance cytometry at high throughput (∼350 cells/s) to measure the electrical phenotype of single PDAC tumor cells from xenografts, which are derived from primary pancreatic tumors versus those from liver metastases of different patients. A novel phase contrast metric based on variations in the high and low frequency impedance phase responses that is related to electrophysiology of the cell interior is found to be systematically altered as a function of tumorigenicity. PDAC cells of higher tumorigenicity exhibited lowered interior conductivity and enhanced permittivity, which is validated by the dielectrophoresis on the respective cell types. Using genetic analysis, we suggest the role of dysregulated Na+ transport and removal of Ca2+ ions from the cytoplasm on key oncogenic KRAS-driven processes that may be responsible for lowering of the interior cell conductivity. We envision that impedance cytometry can serve as a tool to quantify phenotypic heterogeneity for rapidly stratifying tumorigenicity. It can also aid in protocols for dielectrophoretic isolation of cells with a particular phenotype for prognostic studies on patient survival and to tailor therapy selection to specific patients.
- Subjects :
- Cell type
Microfluidics
Cell
02 engineering and technology
Adenocarcinoma
01 natural sciences
Biochemistry
Article
Analytical Chemistry
Proto-Oncogene Proteins p21(ras)
Mice
Cell Line, Tumor
Electric Impedance
medicine
Animals
Humans
Environmental Chemistry
Pancreas
Gene
Spectroscopy
Genetic heterogeneity
Chemistry
010401 analytical chemistry
021001 nanoscience & nanotechnology
Phenotype
0104 chemical sciences
Electrophysiology
Gene Expression Regulation, Neoplastic
medicine.anatomical_structure
Liver
Cytoplasm
Cancer research
Heterografts
Single-Cell Analysis
0210 nano-technology
Cytometry
Carcinoma, Pancreatic Ductal
Subjects
Details
- ISSN :
- 00032670
- Volume :
- 1101
- Database :
- OpenAIRE
- Journal :
- Analytica Chimica Acta
- Accession number :
- edsair.doi.dedup.....202b6f016f29ec3f6c8fde55d853dd59