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Radiofrequency treatment alters cancer cell phenotype.

Ware MJ, Tinger S, Colbert KL, Corr SJ, Rees P, Koshkina N, Curley S, Summers HD, Godin B - Sci Rep (2015)

Bottom Line: These characteristics are intrinsically different between malignant and non-malignant cells and change in response to therapy or in the progression of the disease.Our data show that cell topography, morphology, motility, adhesion and division change as a result of the treatment.Clear phenotypical differences were observed between cancerous and normal cells in both their untreated states and in their response to RF therapy.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, USA [2] Centre for Nanohealth, College of Engineering, Swansea University, Swansea, UK.

ABSTRACT
The importance of evaluating physical cues in cancer research is gradually being realized. Assessment of cancer cell physical appearance, or phenotype, may provide information on changes in cellular behavior, including migratory or communicative changes. These characteristics are intrinsically different between malignant and non-malignant cells and change in response to therapy or in the progression of the disease. Here, we report that pancreatic cancer cell phenotype was altered in response to a physical method for cancer therapy, a non-invasive radiofrequency (RF) treatment, which is currently being developed for human trials. We provide a battery of tests to explore these phenotype characteristics. Our data show that cell topography, morphology, motility, adhesion and division change as a result of the treatment. These may have consequences for tissue architecture, for diffusion of anti-cancer therapeutics and cancer cell susceptibility within the tumor. Clear phenotypical differences were observed between cancerous and normal cells in both their untreated states and in their response to RF therapy. We also report, for the first time, a transfer of microsized particles through tunneling nanotubes, which were produced by cancer cells in response to RF therapy. Additionally, we provide evidence that various sub-populations of cancer cells heterogeneously respond to RF treatment.

No MeSH data available.


Related in: MedlinePlus

Whole cell population analysis 2-D Cell area.a) % cell area (normalized to the cell area before RF) at time points before, 0, 2 and 4 h after RF (n > 600 cells per group). b) Schematic diagram representing increased diffusion of dose (red dots) through cell monolayer after RF treatment (*p < 0.01, **p < 0.05).
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f1: Whole cell population analysis 2-D Cell area.a) % cell area (normalized to the cell area before RF) at time points before, 0, 2 and 4 h after RF (n > 600 cells per group). b) Schematic diagram representing increased diffusion of dose (red dots) through cell monolayer after RF treatment (*p < 0.01, **p < 0.05).

Mentions: Morphological and size parameters of PANC-1, AsPc-1 and HPDE were characterized before and after RF. The brightfield time-lapse data showed PANC-1 and AsPc-1 cells immediately retract their cytoplasm in response to a single RF treatment (Fig. 1, Fig. S1, Supplementary). This suggested the malignant cells had undergone a form of hyperthermal shock (Fig. S2, Supplementary). Non-malignant HPDE cells when subjected to a single RF treatment did not display any significant cytoplasmic retraction or detachment from the substrate surface. Between 0 and 4 h after RF, malignant cells recovered their adhesion to the substrate surface, indicated by their recovery in size, (Fig. 1) and at 24 h full recovery of cell area had occurred. These time-resolved images of a live cell population provide details of the timing of the cellular responses to RF. This will aid in the development of effective treatment schedules in human patients. SEM micrographs showed the hyperthermal shock and subsequent cell area recovery in an increased resolution at 0 h and 24 h after RF, respectively. SEM micrographs also suggested that the morphology of the cell membrane had altered after RF in malignant cell lines, which may influence the interactions of the cells with their environment (including nano- and microparticles). However, since there are numerous factors that affect a variety of bio-physicochemical processes at the nano-bio interface16, we are not able to draw a clear conclusion regarding the influence of the changes in cell surface roughness on the uptake of nano- and microparticles (Fig. 2a,b and S3, Supplementary). Atomic force microscopy images were obtained to provide topographical data of representative cells before and after RF treatment. AFM topographical data suggest that cell retraction primarily is due to a re-organization of the cytoskeleton and cell membrane rather than an expulsion of cellular contents (Fig. 2c1, c2).


Radiofrequency treatment alters cancer cell phenotype.

Ware MJ, Tinger S, Colbert KL, Corr SJ, Rees P, Koshkina N, Curley S, Summers HD, Godin B - Sci Rep (2015)

Whole cell population analysis 2-D Cell area.a) % cell area (normalized to the cell area before RF) at time points before, 0, 2 and 4 h after RF (n > 600 cells per group). b) Schematic diagram representing increased diffusion of dose (red dots) through cell monolayer after RF treatment (*p < 0.01, **p < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4499808&req=5

f1: Whole cell population analysis 2-D Cell area.a) % cell area (normalized to the cell area before RF) at time points before, 0, 2 and 4 h after RF (n > 600 cells per group). b) Schematic diagram representing increased diffusion of dose (red dots) through cell monolayer after RF treatment (*p < 0.01, **p < 0.05).
Mentions: Morphological and size parameters of PANC-1, AsPc-1 and HPDE were characterized before and after RF. The brightfield time-lapse data showed PANC-1 and AsPc-1 cells immediately retract their cytoplasm in response to a single RF treatment (Fig. 1, Fig. S1, Supplementary). This suggested the malignant cells had undergone a form of hyperthermal shock (Fig. S2, Supplementary). Non-malignant HPDE cells when subjected to a single RF treatment did not display any significant cytoplasmic retraction or detachment from the substrate surface. Between 0 and 4 h after RF, malignant cells recovered their adhesion to the substrate surface, indicated by their recovery in size, (Fig. 1) and at 24 h full recovery of cell area had occurred. These time-resolved images of a live cell population provide details of the timing of the cellular responses to RF. This will aid in the development of effective treatment schedules in human patients. SEM micrographs showed the hyperthermal shock and subsequent cell area recovery in an increased resolution at 0 h and 24 h after RF, respectively. SEM micrographs also suggested that the morphology of the cell membrane had altered after RF in malignant cell lines, which may influence the interactions of the cells with their environment (including nano- and microparticles). However, since there are numerous factors that affect a variety of bio-physicochemical processes at the nano-bio interface16, we are not able to draw a clear conclusion regarding the influence of the changes in cell surface roughness on the uptake of nano- and microparticles (Fig. 2a,b and S3, Supplementary). Atomic force microscopy images were obtained to provide topographical data of representative cells before and after RF treatment. AFM topographical data suggest that cell retraction primarily is due to a re-organization of the cytoskeleton and cell membrane rather than an expulsion of cellular contents (Fig. 2c1, c2).

Bottom Line: These characteristics are intrinsically different between malignant and non-malignant cells and change in response to therapy or in the progression of the disease.Our data show that cell topography, morphology, motility, adhesion and division change as a result of the treatment.Clear phenotypical differences were observed between cancerous and normal cells in both their untreated states and in their response to RF therapy.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, USA [2] Centre for Nanohealth, College of Engineering, Swansea University, Swansea, UK.

ABSTRACT
The importance of evaluating physical cues in cancer research is gradually being realized. Assessment of cancer cell physical appearance, or phenotype, may provide information on changes in cellular behavior, including migratory or communicative changes. These characteristics are intrinsically different between malignant and non-malignant cells and change in response to therapy or in the progression of the disease. Here, we report that pancreatic cancer cell phenotype was altered in response to a physical method for cancer therapy, a non-invasive radiofrequency (RF) treatment, which is currently being developed for human trials. We provide a battery of tests to explore these phenotype characteristics. Our data show that cell topography, morphology, motility, adhesion and division change as a result of the treatment. These may have consequences for tissue architecture, for diffusion of anti-cancer therapeutics and cancer cell susceptibility within the tumor. Clear phenotypical differences were observed between cancerous and normal cells in both their untreated states and in their response to RF therapy. We also report, for the first time, a transfer of microsized particles through tunneling nanotubes, which were produced by cancer cells in response to RF therapy. Additionally, we provide evidence that various sub-populations of cancer cells heterogeneously respond to RF treatment.

No MeSH data available.


Related in: MedlinePlus