Copyright ©The Author(s) 2016.
World J Gastroenterol. Aug 28, 2016; 22(32): 7203-7214
Published online Aug 28, 2016. doi: 10.3748/wjg.v22.i32.7203
Table 1 List of experimental studies investigating the effect of external pressure on colon cancer cells proliferation
Ref.Applied loadPressure loading system and experimental conditionsResults
Hirokawa et al[44], 199740-120 mmHg (5-16 kPa)The pressure-loading apparatus consists of a flask of which cap was pierced and connected to a tubing by which compressed He gas was introduced to raise internal pressure.Pressurization from 40 to 120 mmHg for 48 h significantly increased cell (IEC18) number with peak proliferation at 80 mmHg. Pressure-induced DNA synthesis was further enhanced by the addition of interleukin-2, suggesting the regulation of intestinal epithelial growth by pressure could be dependent on cytokines.
Hirokawa et al[43], 2001Applied pressure for 48 h induced proliferation of IEC18 cell, with a significantly peak at 80 mmHg. The pattern of F-actin distribution was not significantly altered. The pressure-induced increase in phosphorylation of Elk-1 fusion protein corresponding to the activation of MAPK.
Basson et al[63], 200015 mmHg (2 kPa)Cell plates was positioned in an airtight acrylic box, in which pressurized gas was introduced by a tubing to increase pressure.Increasing ambient pressure stimulated the adhesion of human Caco-2, SW1116, SW620, and HT-29 cells to Matrigel, type I collagen, laminin, and fibronectin.
Whitehead et al[6], 20080.8 kPaA controlled mechanical strain was applied on short segments of colon explants obtained from normal and APC1638N/+ mice. Tissues were placed into a mechanical deformation box and compressed in the z-direction of approximately half of their relaxed thickness for 20 min.APC1638N/+ mice showed the expression of the two oncogenes Myc and Twist1, not observed in wild-type colon explants. Myc and Twist1 activation was found to be correlated with an increased presence of nuclear β-catenin . Almost no nuclear β-catenin was detected in the wild-type colon epithelium.
The mechanical stimulation of APC1638N/+ tissue leads to the phosphorylation of β-catenin at tyrosine 654, the site of interaction with E-cadherin, affecting cell adhesions properties.
Fernández-Sánchez et al[5], 20151.2 kPaA controlled pressure was applied in vivo in APC1638N/+ and control mice by subcutaneously inserting a magnet close to the mouse colon. The magnet generates a magnetic force on ultra-magnetic liposomes, stabilized in the mesenchymal cells of the connective tissue surrounding colonic crypts.The magnetically induced load led to a rapid Ret activation and the phosphorylation of β-catenin on Tyr654, impairing its interaction with E-cadherin.
β-catenin nuclear translocation was observed after 15 days with a consequent increased expression of β-catenin-target genes at 1 month, together with crypt enlargement accompanying the formation of early tumorous aberrant crypt foci.
Such malignant behavior was induced in, both, APC1638N/+ and control mice, irrespective of the presence of prior genetic abnormalities.
Avvisato et al[27], 20071.5 kPaCells were plated on 38 mm × 76 mm slides and subjected to a laminar shear stress in a rectangular flow channel for 12 h.β-catenin signalling of SW480 cells decreased to 22% of control values. The β-catenin signalling were measured for 0-24 h during shear stress exposure, it decreased significantly following 12 h of flow, reaching a minimum after 24 h.
Table 2 List of cell properties that depends on substrate stiffness
Substrate-related mechanical propertiesSubstrate stiffnessSubstrate type and compositionOutcomesRelated-biochemical and genetic pathwayRef.
E-to-R transition1 kPaLamininThe E to R transition is not observed.Not applicable.Tang et al[24], 2015
or fibronectin coated PA gel
21 kPaLaminin coated PA gelApproximately 70%-90% of E cells start transiting to R cells after culturing for 7 d. Transition takes approximately 5-10 h.E-Cadherin decreases in dissociated
R cell by a factor 4.73 ± 1.4.
Fibronectin coated PA gelApproximately 70%-90% of E cells start transiting to R cells after culturing for 15 d. Transition takes approximately 5-10 h.Replanted cells retain their dissociated phenotype irrespective of the substrate stiffness.
3.6 GPaFibronectin coated PA gelNot observed.Not applicable.
20 kPaE-cadherin coated PA gelE cells transit to R cells in 6 h.Vinculin in mainly located at the cell-cell junction.
Fibronectin coated PA gelE cells transit to R cells in 6 h.Vinculin in mainly located at the cell- substrate junction.Ali et al[45], 2014
~70 GPaE-cadherin coated stiff glass substratesTransition is not observed.Not applicable.
Extremely stiff1Plastic/glass stiff substrateOccasionally E cells transit to R cell (1 cell over 2 × 105).R cells are deficient in αE-catenin (protein linking the cell-cell adhesion molecule E-cadherin to the action cytoskeleton).Vermeulen et al[46-48], 1995, 1998, 1999
Cell colony sizes1-20 kPaGradient stiffness fibronectin coated PA gelE type: colony size positively correlated with substrate stiffnessNot applicable.Tang et al[25], 2012
R type: colony size (smaller than E-colony size) positively correlated with substrate stiffness.
Soft1Agar gelEqual numbers of E and R cells were plated and examined after 10 d, 75% of the E cells plated formed colonies while R cells formed no colonies.Rosenthal et al[72], 1977
Adhesion1-20 kPaGradient stiffness fibronectin coated PA gelE type: cells show a strong cell-cell adhesion and cell-substrate adhesion evaluated through the measurement of the cell-substrate contact area (188.1 ± 80.7 μm2) by confocal microscopy. Moreover, a strong aspecific adhesion of ~250 nN is detected trough a novel MEMS system.Reduced E-cadherin expression on R cells.Tang et al[25], 2012
R type: cells show a weak cell-cell adhesion on very soft substrate (1 kPa). No cell-cell contact is observed on stiffer substrate (5-10-15-20 kPa). A weak cell/substrate adhesion is demonstrated through the measurement of the cell/surface contact area (49.5 ± 20.9 μm2).
A week aspecific adhesion of ~2.5 nN is measured through a MEMS system.