Effects of increased hydrostatic pressure on cell migration:Roles of Aquaporin1 (AQP1) activation
Date Issued
2015
Date
2015
Author(s)
Cheng, Chu-Jung
Abstract
Mechanical cues from microenvironment of cells have a great influence on the cell’s behaviors. Many solid tumors are characterized by high interstitial fluid pressure (IFP), which leads to a reduced uptake of therapeutic drugs or antibodies into the tumors and results in a significant obstacle in cancer therapy. However, whether the increased IFP plays a direct role in behaviors of cancer cells remains unclear. Understanding of relationships between the increased IFP and cancer cell’s behaviors holds the promise of improvement of strategies for cancer therapy. In this work, we developed a cell-culturing system that imposed various hydrostatic pressures (HPs) ranging from 0 to 20 mmHg on cultured cells to simulate the increased IFP and examined the changes in cell’s behaviors. We found that high HP enhances the migration speed, spreading area, number of filopodia, and volume of individual lung cancer cells. By contrast, those changes in normal lung cells were not significant after exposure to high HP. Biochemical studies using western blotting revealed that high HP promoted motility of lung cancer cells via ERK1/2-mediated activation of aquaporin-1 (AQP1), whereas high HP elicited minimal changes in cell motility and morphology in normal lung cells. Our data indicate that high HPs significantly change the invasiveness of lung cancer cells and highlighted the role of ERK1/2-dependent activation of AQP1 in these changes.
Subjects
Cell migration
Hydrostatic pressures
Interstitial fluid pressure
Lung cancer cell
Lung normal cell
Aquaporin1
ERK1/2
SDGs
Type
thesis
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