Abstract
The relationship between chronic inflammation and cancer is well known. The inflammation increases the permeability of blood vessels and consequently elevates pressure in the interstitial tissues. However, there have been only a few reports on the effects of hydrostatic pressure on cultured cells, and the relationship between elevated hydrostatic pressure and cell properties related to malignant tumors is less well understood. Therefore, we investigated the effects of hydrostatic pressure on the cultured epithelial cells seeded on permeable filters. Surprisingly, hydrostatic pressure from basal to apical side induced epithelial stratification in Madin-Darby canine kidney (MDCK) I and Caco-2 cells, and cavities with microvilli and tight junctions around their surfaces were formed within the multi-layered epithelia. The hydrostatic pressure gradient also promoted cell proliferation, suppressed cell apoptosis, and increased transepithelial ion permeability. The inhibition of protein kinase A (PKA) promoted epithelial stratification by the hydrostatic pressure whereas the activation of PKA led to suppressed epithelial stratification. These results indicate the role of the hydrostatic pressure gradient in the regulation of various epithelial cell functions. The findings in this study may provide clues for the development of a novel strategy for the treatment of the carcinoma.
Highlights
The relationship between chronic inflammation and cancer is well known [1]; epidemiological studies have shown that chronic inflammation predisposes individuals to various types of cancer, and inflammatory cells and inflammatory mediators, such as chemokines, cytokines, and transcription factors, have been reported to be involved in the pathways that link inflammation and cancer [2,3,4]
The values of transepithelial electrical resistance (TER) in Madin-Darby canine kidney (MDCK) I cells at two days after seeding were higher than 1000 OÁcm2, which indicated an establishment of confluent epithelial cell sheets
A multi-layered cell sheet was observed in the case of Caco-2 cells under the ‘Basal’ condition (Fig 2F, 2G and 2H). These results indicate that the epithelial stratification induced by the hydrostatic pressure from basal to apical side is not a specific phenomenon to MDCK I cells and occurs in Caco-2 cells, and responsiveness to the hydrostatic pressure varies depending on the cell types
Summary
The relationship between chronic inflammation and cancer is well known [1]; epidemiological studies have shown that chronic inflammation predisposes individuals to various types of cancer, and inflammatory cells and inflammatory mediators, such as chemokines, cytokines, and transcription factors, have been reported to be involved in the pathways that link inflammation and cancer [2,3,4]. Under the ‘Increase’ condition, a single layer of the cell sheet was observed similar to that of the ‘Apical’ condition (Fig 2A), indicating that the increase in the culture medium in the basal side does not trigger epithelial stratification when the culture medium is not decreased in the apical side.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
