scholarly journals Apolar and polar transitions drive the conversion between amoeboid and mesenchymal shapes in melanoma cells

2015 ◽  
Vol 26 (22) ◽  
pp. 4163-4170 ◽  
Author(s):  
Sam Cooper ◽  
Amine Sadok ◽  
Vicky Bousgouni ◽  
Chris Bakal
Keyword(s):  
Quantitative Imaging ◽  
Three Dimensional ◽  
Shape Space ◽  
Melanoma Cells ◽  
Collagen Matrices ◽  
Morphological Heterogeneity ◽  
Rho Family Gtpases ◽  
Metastatic Process ◽  
Rho Family ◽  
Single Living

Melanoma cells can adopt two functionally distinct forms, amoeboid and mesenchymal, which facilitates their ability to invade and colonize diverse environments during the metastatic process. Using quantitative imaging of single living tumor cells invading three-dimensional collagen matrices, in tandem with unsupervised computational analysis, we found that melanoma cells can switch between amoeboid and mesenchymal forms via two different routes in shape space—an apolar and polar route. We show that whereas particular Rho-family GTPases are required for the morphogenesis of amoeboid and mesenchymal forms, others are required for transitions via the apolar or polar route and not amoeboid or mesenchymal morphogenesis per se. Altering the transition rates between particular routes by depleting Rho-family GTPases can change the morphological heterogeneity of cell populations. The apolar and polar routes may have evolved in order to facilitate conversion between amoeboid and mesenchymal forms, as cells are either searching for, or attracted to, particular migratory cues, respectively.

scholarly journals NecroX-5 Can Suppress Melanoma Metastasis by Reducing the Expression of Rho-Family GTPases

2021 ◽  
Vol 10 (13) ◽  
pp. 2790
Author(s):  
Gue-Tae Moon ◽  
Ji-Hyun Lee ◽  
Sang-Hyun Jeong ◽  
Song-Wan Jin ◽  
Young-Min Park
Keyword(s):  
Cell Lines ◽  
Melanoma Cell ◽  
Cancer Metastasis ◽  
Melanoma Cells ◽  
Untreated Group ◽  
Melanoma Metastasis ◽  
Rho Family Gtpases ◽  
Melanoma Model ◽  
Rho Family ◽  
Melanoma Cell Lines

NecroX-5 (NX-5) is a cell-permeable necrosis inhibitor with cytoprotective effects. Although it has been reported to inhibit lung and breast cancer metastasis by modulating migration, its therapeutic effect on melanoma metastasis is still unknown. In this study, we examined the anti-metastatic effect of NX-5 on melanoma cell lines and its related therapeutic mechanism. The anti-metastatic effect of NX-5 on melanoma cell lines was determined using a transwell migration assay. We performed a quantitative real-time polymerase chain reaction and western blot analysis to measure changes in the expression of mRNA and protein, respectively, for major mediators of Rho-family GTPases after NX-5 treatment in melanoma cells. In addition, after constructing the 3D melanoma model, the expression of Rho-family GTPases was measured by immunohistochemistry. NX-5 (10 μM and 20 μM) treatment significantly reduced melanoma cell migration (p < 0.01). Additionally, NX-5 (20 μM) treatment significantly decreased the mRNA and protein expression levels of Cdc42, Rac1, and RhoA in melanoma cells compared with the untreated group (p < 0.001 and p < 0.05, respectively). Immunohistochemistry for our 3D melanoma model showed that Cdc42, Rac1, and RhoA were constitutively expressed in the nuclei of melanoma cells of the untreated group, and NX-5 treatment decreased their expression. These results demonstrate that NX-5 can suppress melanoma metastasis by reducing the expression of Rho-family GTPases.

scholarly journals The Rho family GEF Asef2 regulates cell migration in three dimensional (3D) collagen matrices through myosin II

2014 ◽  
Vol 8 (5) ◽  
pp. 460-467 ◽  
Author(s):  
Léolène Jean ◽  
Lijie Yang ◽  
Devi Majumdar ◽  
Yandong Gao ◽  
Mingjian Shi ◽  
...  
Keyword(s):  
Cell Migration ◽  
Myosin Ii ◽  
Three Dimensional ◽  
Collagen Matrices ◽  
3D Collagen ◽  
Rho Family

The role of Rho-family GTPases in human glioblastomas

2004 ◽  
Vol 31 (S 1) ◽  
Author(s):  
S Seta ◽  
M Herr ◽  
S Horn ◽  
D Koch ◽  
T Vogt ◽  
...  
Keyword(s):  
Rho Family Gtpases ◽  
Rho Family

scholarly journals Dendritic Fibroblasts in Three-dimensional Collagen Matrices

2003 ◽  
Vol 14 (2) ◽  
pp. 384-395 ◽  
Author(s):  
Frederick Grinnell ◽  
Chin-Han Ho ◽  
Elisa Tamariz ◽  
David J. Lee ◽  
Gabriella Skuta
Keyword(s):  
Dimensional Space ◽  
Human Fibroblasts ◽  
Three Dimensional ◽  
Rho Kinase ◽  
Matrix Remodeling ◽  
Dependent Manner ◽  
Collagen Matrices ◽  
Form And Function ◽  
Metabolic Coupling ◽  
Dendritic Network

Cell motility determines form and function of multicellular organisms. Most studies on fibroblast motility have been carried out using cells on the surfaces of culture dishes. In situ, however, the environment for fibroblasts is the three-dimensional extracellular matrix. In the current research, we studied the morphology and motility of human fibroblasts embedded in floating collagen matrices at a cell density below that required for global matrix remodeling (i.e., contraction). Under these conditions, cells were observed to project and retract a dendritic network of extensions. These extensions contained microtubule cores with actin concentrated at the tips resembling growth cones. Platelet-derived growth factor promoted formation of the network; lysophosphatidic acid stimulated its retraction in a Rho and Rho kinase-dependent manner. The dendritic network also supported metabolic coupling between cells. We suggest that the dendritic network provides a mechanism by which fibroblasts explore and become interconnected to each other in three-dimensional space.

scholarly journals R-cadherin influences cell motility via Rho family GTPases. Vol. 279 (2004) 31041-31049

2004 ◽  
Vol 279 (42) ◽  
pp. 44229-44230
Author(s):  
Emhonta Johnson ◽  
Christopher S. Theisen ◽  
Keith R. Johnson ◽  
Margaret J. Wheelock
Keyword(s):  
Cell Motility ◽  
Rho Family Gtpases ◽  
Rho Family

scholarly journals Three-dimensional relationships between tumor cells and microcirculation with double cyanine immunolabeling, laser scanning confocal microscopy, and computer-assisted reconstruction: an alternative to cast corrosion preparations.

1994 ◽  
Vol 42 (5) ◽  
pp. 681-686 ◽  
Author(s):  
V Rummelt ◽  
L M Gardner ◽  
R Folberg ◽  
S Beck ◽  
B Knosp ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Blood Vessels ◽  
Tumor Cells ◽  
Laser Scanning ◽  
Three Dimensional ◽  
Melanoma Cells ◽  
Tumor Blood Vessels ◽  
The Relationship ◽  
Scanning Electron

The morphology of the microcirculation of uveal melanomas is a reliable market of tumor progression. Scanning electron microscopy of cast corrosion preparations can generate three-dimensional views of these vascular patterns, but this technique sacrifices the tumor parenchyma. Formalin-fixed wet tissue sections 100-150 microns thick from uveal melanomas were stained with the lectin Ulex europaeus agglutinin I (UEAI) and proliferating cell nuclear antigen (PCNA) to demonstrate simultaneously the tumor blood vessels and proliferating tumor cells. Indocarbocyanine (Cy3) was used as a fluorophore for UEAI and indodicarbocyanine (Cy5) was used for PCNA. Double labeled sections were examined with a laser scanning confocal microscope. Images of both stains were digitized at the same 5-microns intervals and each of the two images per interval was combined digitally to form one image. These combined images were visualized through voxel processing to study the relationship between melanoma cells expressing PCNA and various microcirculatory patterns. This technique produces images comparable to scanning electron microscopy of cast corrosion preparations while permitting simultaneous localization of melanoma cells expressing PCNA. The microcirculatory tree can be viewed from any perspective and the relationship between tumor cells and the tumor blood vessels can be studied concurrently in three dimensions. This technique is an alternative to cast corrosion preparations.

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