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Effects of Hydrostatic Pressure on Carcinogenic Properties of Epithelia.

Tokuda S, Kim YH, Matsumoto H, Muro S, Hirai T, Mishima M, Furuse M - PLoS ONE (2015)

Bottom Line: 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.The findings in this study may provide clues for the development of a novel strategy for the treatment of the carcinoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

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.

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Effects of signal inhibitors and activators on the epithelial stratification by the hydrostatic pressure.(A) Light microscopic images in a vertical section under the ‘Apical’ condition in the presence of the signal inhibitor or activator in MDCK I cells. The upper side is apical side and the lower side is basal side. (B) Stratification index of MDCK I cells under the ‘Apical’ condition in the presence of the signal inhibitor or activator. The stratification index in the presence of H89 and SQ22536 was significantly higher than that in the control experiment (DMSO). (C) Light microscopic images in a vertical section under the ‘Basal’ condition in the presence of the signal inhibitor or activator in MDCK I cells. The upper side is apical side and the lower side is basal side. (D) Stratification index of MDCK I cells under the ‘Basal’ condition in the presence of the signal inhibitor or activator. The administration of H89 significantly increased the degree of epithelial stratification by the hydrostatic pressure, and the administration of forskolin significantly decreased the degree of the epithelial stratification. ** p < 0.01 compared with control (DMSO).
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pone.0145522.g012: Effects of signal inhibitors and activators on the epithelial stratification by the hydrostatic pressure.(A) Light microscopic images in a vertical section under the ‘Apical’ condition in the presence of the signal inhibitor or activator in MDCK I cells. The upper side is apical side and the lower side is basal side. (B) Stratification index of MDCK I cells under the ‘Apical’ condition in the presence of the signal inhibitor or activator. The stratification index in the presence of H89 and SQ22536 was significantly higher than that in the control experiment (DMSO). (C) Light microscopic images in a vertical section under the ‘Basal’ condition in the presence of the signal inhibitor or activator in MDCK I cells. The upper side is apical side and the lower side is basal side. (D) Stratification index of MDCK I cells under the ‘Basal’ condition in the presence of the signal inhibitor or activator. The administration of H89 significantly increased the degree of epithelial stratification by the hydrostatic pressure, and the administration of forskolin significantly decreased the degree of the epithelial stratification. ** p < 0.01 compared with control (DMSO).

Mentions: Then we investigated the effects of the inhibitors and activators on the epithelial stratification by the hydrostatic pressure. We seeded MDCK I cells on filters, and two days after seeding, we applied hydrostatic pressure in the presence of the inhibitor or activator. Surprisingly, the administration of H89, a PKA inhibitor, induced a slight degree of epithelial stratification even under the ‘Apical’ condition (Fig 12A and 12B). The administration of SQ22536, which decreases the intracellular levels of cAMP and results in the inhibition of PKA, also induced a slight degree of epithelial stratification under the ‘Apical’ condition. In contrast, a single layer of MDCK I cell sheet was observed in the presence of Go6983, genistein, forskolin and IBMX similar to the control experiment (DMSO) under the ‘Apical’ condition (Fig 12A and 12B).


Effects of Hydrostatic Pressure on Carcinogenic Properties of Epithelia.

Tokuda S, Kim YH, Matsumoto H, Muro S, Hirai T, Mishima M, Furuse M - PLoS ONE (2015)

Effects of signal inhibitors and activators on the epithelial stratification by the hydrostatic pressure.(A) Light microscopic images in a vertical section under the ‘Apical’ condition in the presence of the signal inhibitor or activator in MDCK I cells. The upper side is apical side and the lower side is basal side. (B) Stratification index of MDCK I cells under the ‘Apical’ condition in the presence of the signal inhibitor or activator. The stratification index in the presence of H89 and SQ22536 was significantly higher than that in the control experiment (DMSO). (C) Light microscopic images in a vertical section under the ‘Basal’ condition in the presence of the signal inhibitor or activator in MDCK I cells. The upper side is apical side and the lower side is basal side. (D) Stratification index of MDCK I cells under the ‘Basal’ condition in the presence of the signal inhibitor or activator. The administration of H89 significantly increased the degree of epithelial stratification by the hydrostatic pressure, and the administration of forskolin significantly decreased the degree of the epithelial stratification. ** p < 0.01 compared with control (DMSO).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4696811&req=5

pone.0145522.g012: Effects of signal inhibitors and activators on the epithelial stratification by the hydrostatic pressure.(A) Light microscopic images in a vertical section under the ‘Apical’ condition in the presence of the signal inhibitor or activator in MDCK I cells. The upper side is apical side and the lower side is basal side. (B) Stratification index of MDCK I cells under the ‘Apical’ condition in the presence of the signal inhibitor or activator. The stratification index in the presence of H89 and SQ22536 was significantly higher than that in the control experiment (DMSO). (C) Light microscopic images in a vertical section under the ‘Basal’ condition in the presence of the signal inhibitor or activator in MDCK I cells. The upper side is apical side and the lower side is basal side. (D) Stratification index of MDCK I cells under the ‘Basal’ condition in the presence of the signal inhibitor or activator. The administration of H89 significantly increased the degree of epithelial stratification by the hydrostatic pressure, and the administration of forskolin significantly decreased the degree of the epithelial stratification. ** p < 0.01 compared with control (DMSO).
Mentions: Then we investigated the effects of the inhibitors and activators on the epithelial stratification by the hydrostatic pressure. We seeded MDCK I cells on filters, and two days after seeding, we applied hydrostatic pressure in the presence of the inhibitor or activator. Surprisingly, the administration of H89, a PKA inhibitor, induced a slight degree of epithelial stratification even under the ‘Apical’ condition (Fig 12A and 12B). The administration of SQ22536, which decreases the intracellular levels of cAMP and results in the inhibition of PKA, also induced a slight degree of epithelial stratification under the ‘Apical’ condition. In contrast, a single layer of MDCK I cell sheet was observed in the presence of Go6983, genistein, forskolin and IBMX similar to the control experiment (DMSO) under the ‘Apical’ condition (Fig 12A and 12B).

Bottom Line: 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.The findings in this study may provide clues for the development of a novel strategy for the treatment of the carcinoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

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.

Show MeSH
Related in: MedlinePlus