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Electric Cell-Substrate Impedance Sensing (ECIS) with Microelectrode Arrays for Investigation of Cancer Cell-Fibroblasts Interaction.

Tran TB, Baek C, Min J - PLoS ONE (2016)

Bottom Line: In brief, a co-culture device consisting of 2 individual fluidic chambers in parallel, which were separated by a 100 μm fence was utilized for cell patterning.Microelectrodes arrays were installed within each chamber including electrodes at various distances away from the confrontation line for the electrochemical impedimetric sensing assessment of cell-to-cell influence.After the fence was removed and cell-to-cell contact occurred, by evaluating the impedance signal responses representing cell condition and behavior, both direct and indirect cell-to-cell interactions through conditioned media were investigated.

View Article: PubMed Central - PubMed

Affiliation: School of Integrative Engineering, Chung-Ang University, Heukseok-dong, Dongjak-gu, Seoul, Republic of Korea.

ABSTRACT
The tumor microenvironment, including stromal cells, surrounding blood vessels and extracellular matrix components, has been defined as a crucial factor that influences the proliferation, drug-resistance, invasion and metastasis of malignant epithelial cells. Among other factors, the communications and interaction between cancer cells and stromal cells have been reported to play pivotal roles in cancer promotion and progression. To investigate these relationships, an on-chip co-culture model was developed to study the cellular interaction between A549-human lung carcinoma cells and MRC-5-human lung epithelial cells in both normal proliferation and treatment conditions. In brief, a co-culture device consisting of 2 individual fluidic chambers in parallel, which were separated by a 100 μm fence was utilized for cell patterning. Microelectrodes arrays were installed within each chamber including electrodes at various distances away from the confrontation line for the electrochemical impedimetric sensing assessment of cell-to-cell influence. After the fence was removed and cell-to-cell contact occurred, by evaluating the impedance signal responses representing cell condition and behavior, both direct and indirect cell-to-cell interactions through conditioned media were investigated. The impact of specific distances that lead to different influences of fibroblast cells on cancer cells in the co-culture environment was also defined.

No MeSH data available.


Related in: MedlinePlus

Summary of A549 cell viability as a function of co-culture time and distance from fibroblasts over 72 h in the curcumin treatment condition.
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pone.0153813.g006: Summary of A549 cell viability as a function of co-culture time and distance from fibroblasts over 72 h in the curcumin treatment condition.

Mentions: This study was aimed to propose a simple but effective method to investigate the interactions of tumor cells and fibroblasts in a co-culture model, with specific focus on the distance effect between these 2 cell lines. The overall inhibitory and toxic effects on A549 cancer cells are shown in Fig 6. It should be noted that other previous studies have examined the inhibition of tumor cell proliferation and motility by fibroblasts [28–31]; the common conclusion was that the inhibition effect was both contact- and soluble factor-dependent. However, the effective distance between tumor cells and fibroblasts had not yet been determined. By integrating an MEA platform into a co-culture model, we successfully determined the differences of A549 tumor cell behaviors at various distances away from MRC-5 fibroblasts in both normal proliferation and treatment conditions. Our results showed that the influences on the tumor cells could be categorized into 3 different zones based on the viability of the tumor cells. The first zone was located up to 0.25 mm away from the fibroblast confrontation line, where cancer cells were strongly inhibited in both normal and toxic conditions. This result can be explained by the involvement of the surface molecules of fibroblasts as well as the soluble factors that are secreted because of the confrontation between fibroblasts and tumor cells [31]. The second zone was located up to 3 mm away from the first zone, where the effect in normal growth conditions was indistinct but was clearly demonstrated in the treatment condition. This result can also be explained by the soluble factors secreted from fibroblasts from a limited distance. The third zone encompassed the remaining area. In the normal co-cultures, the A549 tumor cells in this zone maintained CI values of 6.6 and 6.5, which indicated a normal proliferation rate despite the cross-talk of distant cells. In the treatment condition, A549 cell viability was determined to be 75.6%, which was approximately the same value determined by the mitochondrial based MTS assay (72.1%). This equivalence obviously indicated that conditioned media did not cause any inhibitory effect when the cancer cells were more than 3 mm away from the fibroblasts.


Electric Cell-Substrate Impedance Sensing (ECIS) with Microelectrode Arrays for Investigation of Cancer Cell-Fibroblasts Interaction.

Tran TB, Baek C, Min J - PLoS ONE (2016)

Summary of A549 cell viability as a function of co-culture time and distance from fibroblasts over 72 h in the curcumin treatment condition.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835071&req=5

pone.0153813.g006: Summary of A549 cell viability as a function of co-culture time and distance from fibroblasts over 72 h in the curcumin treatment condition.
Mentions: This study was aimed to propose a simple but effective method to investigate the interactions of tumor cells and fibroblasts in a co-culture model, with specific focus on the distance effect between these 2 cell lines. The overall inhibitory and toxic effects on A549 cancer cells are shown in Fig 6. It should be noted that other previous studies have examined the inhibition of tumor cell proliferation and motility by fibroblasts [28–31]; the common conclusion was that the inhibition effect was both contact- and soluble factor-dependent. However, the effective distance between tumor cells and fibroblasts had not yet been determined. By integrating an MEA platform into a co-culture model, we successfully determined the differences of A549 tumor cell behaviors at various distances away from MRC-5 fibroblasts in both normal proliferation and treatment conditions. Our results showed that the influences on the tumor cells could be categorized into 3 different zones based on the viability of the tumor cells. The first zone was located up to 0.25 mm away from the fibroblast confrontation line, where cancer cells were strongly inhibited in both normal and toxic conditions. This result can be explained by the involvement of the surface molecules of fibroblasts as well as the soluble factors that are secreted because of the confrontation between fibroblasts and tumor cells [31]. The second zone was located up to 3 mm away from the first zone, where the effect in normal growth conditions was indistinct but was clearly demonstrated in the treatment condition. This result can also be explained by the soluble factors secreted from fibroblasts from a limited distance. The third zone encompassed the remaining area. In the normal co-cultures, the A549 tumor cells in this zone maintained CI values of 6.6 and 6.5, which indicated a normal proliferation rate despite the cross-talk of distant cells. In the treatment condition, A549 cell viability was determined to be 75.6%, which was approximately the same value determined by the mitochondrial based MTS assay (72.1%). This equivalence obviously indicated that conditioned media did not cause any inhibitory effect when the cancer cells were more than 3 mm away from the fibroblasts.

Bottom Line: In brief, a co-culture device consisting of 2 individual fluidic chambers in parallel, which were separated by a 100 μm fence was utilized for cell patterning.Microelectrodes arrays were installed within each chamber including electrodes at various distances away from the confrontation line for the electrochemical impedimetric sensing assessment of cell-to-cell influence.After the fence was removed and cell-to-cell contact occurred, by evaluating the impedance signal responses representing cell condition and behavior, both direct and indirect cell-to-cell interactions through conditioned media were investigated.

View Article: PubMed Central - PubMed

Affiliation: School of Integrative Engineering, Chung-Ang University, Heukseok-dong, Dongjak-gu, Seoul, Republic of Korea.

ABSTRACT
The tumor microenvironment, including stromal cells, surrounding blood vessels and extracellular matrix components, has been defined as a crucial factor that influences the proliferation, drug-resistance, invasion and metastasis of malignant epithelial cells. Among other factors, the communications and interaction between cancer cells and stromal cells have been reported to play pivotal roles in cancer promotion and progression. To investigate these relationships, an on-chip co-culture model was developed to study the cellular interaction between A549-human lung carcinoma cells and MRC-5-human lung epithelial cells in both normal proliferation and treatment conditions. In brief, a co-culture device consisting of 2 individual fluidic chambers in parallel, which were separated by a 100 μm fence was utilized for cell patterning. Microelectrodes arrays were installed within each chamber including electrodes at various distances away from the confrontation line for the electrochemical impedimetric sensing assessment of cell-to-cell influence. After the fence was removed and cell-to-cell contact occurred, by evaluating the impedance signal responses representing cell condition and behavior, both direct and indirect cell-to-cell interactions through conditioned media were investigated. The impact of specific distances that lead to different influences of fibroblast cells on cancer cells in the co-culture environment was also defined.

No MeSH data available.


Related in: MedlinePlus