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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

Tunneling nanotubes (TNTs) formation as a result of RF-treatment.a) and b) RF causes an increase in the formation of Tunneling Nanotubes (TNTs) in malignant cell lines (Red arrows indicate TNTs) (n = 1000, *p < 0.01) (Scale bar = 50 μm). TNTs are thought to be involved in cell-cell signaling and particle trafficking over short-medium distances. c) TNTs are also associated with particle trafficking in cancer cell lines, which, to our knowledge has not been documented before. TNTs may provide a mechanism for transfer of dose throughout a malignant population or may offer cancer cells a mechanism where they are able to dilute a toxic dose to ensure survival. (White scale bar = 20 μm, red scale bar = 1 μm). d) SEM images of TNTs present in 3D pancreatic tumor environment in spheroid models (White scale bar = 3 μm, red scale bar = 5 μm).
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f4: Tunneling nanotubes (TNTs) formation as a result of RF-treatment.a) and b) RF causes an increase in the formation of Tunneling Nanotubes (TNTs) in malignant cell lines (Red arrows indicate TNTs) (n = 1000, *p < 0.01) (Scale bar = 50 μm). TNTs are thought to be involved in cell-cell signaling and particle trafficking over short-medium distances. c) TNTs are also associated with particle trafficking in cancer cell lines, which, to our knowledge has not been documented before. TNTs may provide a mechanism for transfer of dose throughout a malignant population or may offer cancer cells a mechanism where they are able to dilute a toxic dose to ensure survival. (White scale bar = 20 μm, red scale bar = 1 μm). d) SEM images of TNTs present in 3D pancreatic tumor environment in spheroid models (White scale bar = 3 μm, red scale bar = 5 μm).

Mentions: AsPc-1 and PANC-1 displayed a near total retraction of all cellular protrusions, including tunneling nanotubes (TNTs), immediately after RF treatment, which lasted between 0–4 h after exposure. However, overexpression of TNTs (Fig. 4), from the main cell body, occurs from 5 h onwards after RF treatment. TNTs were reported as the means of cell-to-cell interactions, which coordinate the communication between adjacent cells and distant cells in the 3D tissue microenvironment. Although TNTs are present in the healthy cells, pathological conditions (e.g. infectious state, cancer) were previously associated with an increase in the number of TNTs2122. TNTs represent an interesting feature of cells, which, generally, is related to the transfer of information between the two neighboring cells. It is possible that the enhanced expression of TNTs in cells, which underwent RF treatment is a reflection of the stress that the cells experience, similar to what was observed by Feratti and colleagues, who describe an overexpression of TNTs when endothelial cells were cultured in serum free media23.


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)

Tunneling nanotubes (TNTs) formation as a result of RF-treatment.a) and b) RF causes an increase in the formation of Tunneling Nanotubes (TNTs) in malignant cell lines (Red arrows indicate TNTs) (n = 1000, *p < 0.01) (Scale bar = 50 μm). TNTs are thought to be involved in cell-cell signaling and particle trafficking over short-medium distances. c) TNTs are also associated with particle trafficking in cancer cell lines, which, to our knowledge has not been documented before. TNTs may provide a mechanism for transfer of dose throughout a malignant population or may offer cancer cells a mechanism where they are able to dilute a toxic dose to ensure survival. (White scale bar = 20 μm, red scale bar = 1 μm). d) SEM images of TNTs present in 3D pancreatic tumor environment in spheroid models (White scale bar = 3 μm, red scale bar = 5 μm).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Tunneling nanotubes (TNTs) formation as a result of RF-treatment.a) and b) RF causes an increase in the formation of Tunneling Nanotubes (TNTs) in malignant cell lines (Red arrows indicate TNTs) (n = 1000, *p < 0.01) (Scale bar = 50 μm). TNTs are thought to be involved in cell-cell signaling and particle trafficking over short-medium distances. c) TNTs are also associated with particle trafficking in cancer cell lines, which, to our knowledge has not been documented before. TNTs may provide a mechanism for transfer of dose throughout a malignant population or may offer cancer cells a mechanism where they are able to dilute a toxic dose to ensure survival. (White scale bar = 20 μm, red scale bar = 1 μm). d) SEM images of TNTs present in 3D pancreatic tumor environment in spheroid models (White scale bar = 3 μm, red scale bar = 5 μm).
Mentions: AsPc-1 and PANC-1 displayed a near total retraction of all cellular protrusions, including tunneling nanotubes (TNTs), immediately after RF treatment, which lasted between 0–4 h after exposure. However, overexpression of TNTs (Fig. 4), from the main cell body, occurs from 5 h onwards after RF treatment. TNTs were reported as the means of cell-to-cell interactions, which coordinate the communication between adjacent cells and distant cells in the 3D tissue microenvironment. Although TNTs are present in the healthy cells, pathological conditions (e.g. infectious state, cancer) were previously associated with an increase in the number of TNTs2122. TNTs represent an interesting feature of cells, which, generally, is related to the transfer of information between the two neighboring cells. It is possible that the enhanced expression of TNTs in cells, which underwent RF treatment is a reflection of the stress that the cells experience, similar to what was observed by Feratti and colleagues, who describe an overexpression of TNTs when endothelial cells were cultured in serum free media23.

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