These results from Oncotarget show that normoxia and hypoxia have a certain degree of chemotherapeutic drug effects on the biomechanical and biophysical properties of cancer cells distinguishable
Oncotarget published “Dynamic cellular biomechanics in responses to chemotherapeutic drug in hypoxia probed by atomic force spectroscopy”, in which it was reported that the authors used single-cell force spectroscopy methods to determine the biophysical and biomechanical kinetics of the brain, breast and prostate and pancreatic cancer cells with standard chemotherapy drugs for normoxia and hypoxia for 12-24 hours.
After exposure to the drugs, they found that brain, breast, and pancreatic cancer cells became about 55-75% less stiff, while prostate cancer cells became stiffer, either due to a drug-induced disorder or reinforcement of the cytoskeletal structure.
However, the rate of stiffness change in hypoxia decreased up to 2-fold, suggesting a correlation between cellular stiffness and drug resistance of cancer cells in a hypoxic tumor microenvironment.
They also observed significant changes in cell body height, surface roughness, and cytoadhesion of cancer cells after taking drugs, which followed the trend in stiffness.
These oncotarget results show that a degree of chemotherapeutic drug effects on biomechanical and biophysical properties of cancer cells in normoxia and hypoxia are distinguishable, which are correlated with a change in cytoskeletal structure and integrity during the drug-induced apoptotic process.
Dr. Yongki Choi of North Dakota State University said, “The cell surface plays an important role in basic cell functions such as signaling, communication, adhesion, transport and tumor metastasis.”
The cell surfaces interact dynamically with the physical, chemical and biological environments that surround cells, and thus a change in the surface structure of the cell has a significant impact on overall cell functions.
In particular, cell deformability, which is linked to cell shape, motility and invasion, has shown effects on cell death and cancer metastasis, which is important information for the development of new cancer drugs with increased efficacy in cancer chemotherapy.
While a number of studies have shown the relationship between chemotherapy-induced cell death and changes in cell mechanics such as stiffness, the impact of drugs on the biomechanical and biophysical properties of cancer cells is not yet fully understood. In addition, the rigidity at the tissue level is significantly influenced by the tumor stage, the invasiveness and the location within the tumor due to the deposition of extracellular matrix, which also influences the cell behavior and the metastatic capacity at the single cell level.
Several studies with AFM-based force measurements have also shown a significant change in cell stiffness with increasing metastatic efficiency in human cancer cell lines and chemotherapy exposure in leukemia cells.
In this work, these researchers quantified the drug effects on the biomechanical and biophysical properties of four cancer cell lines: MDA-MB-231 triple negative breast cancer, PANC-1 pancreatic cancer, PC-3 prostate cancer, and U-118 MG glioblastoma cell lines.
In its oncotarget research output, the Choi research team concluded that it had investigated changes in biomechanical parameters of cancer cells exposed to an inhibitor of actin polymerization, cytochalasin D, in normoxia and hypoxia.
The PANC-1 cells became less stiff with increasing exposure to cytochalasin D, and the decrease in stiffness was slower in hypoxia than in normoxia.
Morphology and non-specific binding force measurements of the cells exposed to cytochalasin D also showed a reduction in cell height and cell adhesion, but an increase in cell roughness.
Similar changes in the biomechanical properties of other cancer cell lines treated with chemotherapeutic agents and cytochalasin D suggest that the drug-induced cytotoxicity is due in part to dynamic changes in cytoskeletal structure.
Although it is difficult to generalize drug effects on biomechanical and biophysical parameters of cancer cells, a combination of these parameters could help to identify and differentiate the drug-induced apoptotic process in normoxia and hypoxia.
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Correspondence– Yongki Choi – [email protected]
keywords – Cell stiffness, roughness, adhesion, drug resistance, hypoxia
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