Invasive Cx43<sup>high</sup> sub-line of human prostate DU145 cells displays increased nanomechanical deformability

Piwowarczyk, Katarzyna; Sarna, Michał; Ryszawy, Damian; Czyż, Jarosław

doi:10.18388/abp.2017_1593

Cited by 4 publications

(3 citation statements)

References 34 publications

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“…Considering the extent of the effect of melanin on the elastic properties of melanoma cells, particularly on their deformation capabilities, we postulate that in melanoma cells melanin can be viewed as a mechanical inhibitor of the cells metastatic abilities. Of course, other cell parameters, such as the effect of cancer cells on their microenvironment 34 , connexin-formed gap junctions 35 and cell migration 36 , among others, also play an important role in the process of metastasis of melanoma cells. Nevertheless, our findings point to a novel, mechanical role of melanin in melanoma metastasis.…”

Section: Discussionmentioning

confidence: 99%

Melanin presence inhibits melanoma cell spread in mice in a unique mechanical fashion

Sarna

Krzykawska-Serda

Jakubowska

et al. 2019

Sci Rep

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Melanoma is a highly aggressive cancer that exhibits metastasis to various critical organs. Unlike any other cancer cells, melanoma cells can synthesize melanin in large amounts, becoming heavily pigmented. Until now the role of melanin in melanoma, particularly the effect of melanin presence on the abilities of melanoma cells to spread and metastasize remains unknown. Recently, we have shown that melanin dramatically modified elastic properties of melanoma cells and inhibited the cells invasive abilities in vitro . Here, we inoculated human melanoma cells with different melanin content into nude mice and tested the hypothesis that cell elasticity is an important property of cancer cells for their efficient spread in vivo . The obtained results clearly showed that cells containing melanin were less capable to spread in mice than cells without the pigment. Our findings indicate that the presence of melanin inhibits melanoma metastasis, emphasizing possible clinical implications of such an inhibitory effect.

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Section: Discussionmentioning

confidence: 99%

Melanin presence inhibits melanoma cell spread in mice in a unique mechanical fashion

Sarna

Krzykawska-Serda

Jakubowska

et al. 2019

Sci Rep

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“…Based on these observations, we postulated that melanin presence should limit the metastatic abilities of melanoma cells in vivo. Of course, other key cell parameters, such as the effect of cancer cells on their microenvironment [ 38 ], connexin-formed gap junctions [ 39 ] and cell migration [ 40 ] are important in the process of metastasis. However, takin into consideration the magnitude of the mechanical effect of melanin presence on the elasticity of melanoma cells, we strongly believe that cell elasticity may be the most critical parameter responsible for melanoma invasiveness.…”

Section: Discussionmentioning

confidence: 99%

Nanomechanical Phenotype of Melanoma Cells Depends Solely on the Amount of Endogenous Pigment in the Cells

Sarna¹,

Czuba-Pelech²,

Urbańska³

2018

IJMS

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Cancer cells have unique nanomechanical properties, i.e., they behave as if they were elastic. This property of cancer cells is believed to be one of the main reasons for their facilitated ability to spread and metastasize. Thus, the so-called nanomechanical phenotype of cancer cells is viewed as an important indicator of the cells’ metastatic behavior. One of the most highly metastatic cancer cells are melanoma cells, which have a very unusual property: they can synthesize the pigment melanin in large amounts, becoming heavily pigmented. So far, the role of melanin in melanoma remains unclear, particularly the impact of the pigment on metastatic behavior of melanoma cells. Importantly, until recently the potential mechanical role of melanin in melanoma metastasis was completely ignored. In this work, we examined melanoma cells isolated from hamster tumors containing endogenous melanin pigment. Applying an array of advanced microscopy and spectroscopy techniques, we determined that melanin is the dominating factor responsible for the mechanical properties of melanoma cells. Our results indicate that the nanomechanical phenotype of melanoma cells may be a reliable marker of the cells’ metastatic behavior and point to the important mechanical role of melanin in the process of metastasis of melanoma.

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“…The data were pooled and analyzed to estimate the averaged total length of the cell trajectory (i.e., the “Distance” covered by the cells during the registration time; μm) and the total length of cell displacement (“Displacement”, i.e., the distance from the starting point directly to the cell’s final position; µm), and the average speed of cell movement (Speed; μm/min). Cell trajectories from no less than three independent experiments (number of cells > 50) were obtained for analysis [ 49 ]. Instantaneous velocity (V i ) was calculated at each time point ( t ) according to the formula: V i ( t ) = (d 1 + d 2 )/2Δ t , where d 1 and d 2 are the distances travelled during two sequential intervals 1 and 2 (between the frame proceeding and the frame following t , respectively), and Δ t is the time interval between successive frames.…”

Section: Methodsmentioning

confidence: 99%

Fenofibrate Interferes with the Diapedesis of Lung Adenocarcinoma Cells through the Interference with Cx43/EGF-Dependent Intercellular Signaling

Piwowarczyk

Kwiecień

Sośniak

et al. 2018

Cancers

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Extravasation of circulating cancer cells is regulated by the intercellular/intracellular signaling pathways that locally impair the endothelial barrier function. Co-cultures of human umbilical vein endothelial cells (HUVECs) with lung adenocarcinoma A549 cells enabled us to identify these pathways and to quantify the effect of fenofibrate (FF) on their activity. A549 cells induced the disruption and local activation of endothelial continuum. These events were accompanied by epidermal growth factor (EGF) up-regulation in endothelial cells. Impaired A549 diapedesis and HUVEC activation were seen upon the chemical inhibition of connexin(Cx)43 functions, EGF/ERK1/2-dependent signaling, and RhoA/Rac1 activity. A total of 25 μM FF exerted corresponding effects on Cx43-mediated gap junctional coupling, EGF production, and ERK1/2 activation in HUVEC/A549 co-cultures. It also directly augmented endothelial barrier function via the interference with focal adhesion kinase (FAK)/RhoA/Rac1-regulated endothelial cell adhesion/contractility/motility and prompted the selective transmigration of epithelioid A549 cells. N-acetyl-L-cysteine abrogated FF effects on HUVEC activation, suggesting the involvement of PPARα-independent mechanism(s) in its action. Our data identify a novel Cx43/EGF/ERK1/2/FAK/RhoA/Rac1-dependent signaling axis, which determines the efficiency of lung cancer cell diapedesis. FF interferes with its activity and reduces the susceptibility of endothelial cells to A549 stimuli. These findings provide the rationale for the implementation of FF in the therapy of malignant lung cancers.

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Invasive Cx43^high sub-line of human prostate DU145 cells displays increased nanomechanical deformability

Cited by 4 publications

References 34 publications

Melanin presence inhibits melanoma cell spread in mice in a unique mechanical fashion

Melanin presence inhibits melanoma cell spread in mice in a unique mechanical fashion

Nanomechanical Phenotype of Melanoma Cells Depends Solely on the Amount of Endogenous Pigment in the Cells

Fenofibrate Interferes with the Diapedesis of Lung Adenocarcinoma Cells through the Interference with Cx43/EGF-Dependent Intercellular Signaling

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Invasive Cx43high sub-line of human prostate DU145 cells displays increased nanomechanical deformability

Cited by 4 publications

References 34 publications

Melanin presence inhibits melanoma cell spread in mice in a unique mechanical fashion

Melanin presence inhibits melanoma cell spread in mice in a unique mechanical fashion

Nanomechanical Phenotype of Melanoma Cells Depends Solely on the Amount of Endogenous Pigment in the Cells

Fenofibrate Interferes with the Diapedesis of Lung Adenocarcinoma Cells through the Interference with Cx43/EGF-Dependent Intercellular Signaling

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Invasive Cx43^high sub-line of human prostate DU145 cells displays increased nanomechanical deformability