Mechanisms of high interstitial fluid pressure affecting cancer cell motility
Yu-Chiu Kao1*, Huei-Jyuan Pan2, Chu-Jung Cheng1, Po-Ling Kuo1,3, Chau-Hwang Lee4
1Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan
2Research Center for Applied Sciences, Academia Sinica, Taipei, Taiwan
3Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan
4Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan
* presenting author:高于媝, email:winifred@gate.sinica.edu.tw
High interstitial fluid pressure (IFP) is a hallmark of many advanced tumors, but how the raised pressure affects cancer cell motility remains unclear. Here, we investigated the signaling pathways of hydrostatic pressure on the motility of lung cancer cells (CL1-5 and A549). The migration speeds of lung cancer cells were increased by 50–60% when exposed to 20 mmHg pressure for 4 hours. The cellular volumes were also increased by ~50% after 8 hours. We also found that the expression of aquaporin-1 was up-regulated by the pressure. In contrast, normal bronchial epithelial cell (BEAS-2B) did not respond to the pressure shock, suggesting that cancer cells may have evolved the ability to adapt to pressure changes in tumor microenvironment. We have verified that the enhancement in cell motility and the enlargement of cell volume by pressure were both suppressed when the cancer cells were treated by the inhibitor of extracellular regulated protein kinases (ERK). In addition, the ERK inhibitor also removed the increase of aquaporin-1 under the raised pressure.


Keywords: High interstitial fluid pressure (IFP), motility, aquaporin-1, extracellular regulated protein kinases (ERK)