Recent Developments in Electrotaxis Assays

Wu, Jiandong; Lin, Francis

doi:10.1089/wound.2013.0453

Cited by 14 publications

(9 citation statements)

References 28 publications

(17 reference statements)

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“…Electrotaxis (also known as galvanotaxis) is defined as directional migration of cells relative to a direct-current electric field with, depending on the cell type, orientation toward the cathode or the anode [14,[98][99][100][101] (Figure 3B and Table 1). As potential steering mechanisms, the electric field can open voltage-gated Ca 2+ or Na + ion channels followed by intracellular influx of ions and downstream signaling through the activation of ion transport proteins [e.g., Na/K-ATPase, sodium-hydrogen exchanger 3 (NHE3)] and cytoskeletal polarization [99,102].…”

Section: Electrical Guidancementioning

confidence: 99%

Collective cell migration: guidance principles and hierarchies

Haeger

Wolf

Zegers

et al. 2015

Trends in Cell Biology

383

345

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Section: Electrical Guidancementioning

confidence: 99%

Collective cell migration: guidance principles and hierarchies

Haeger

Wolf

Zegers

et al. 2015

Trends in Cell Biology

383

345

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“…Such findings suggest that application of low-magnitude EFs could locally manipulate cell migration within tissues, particularly in the context of nonhealing and chronic wounds, and could be developed as a noninvasive approach to control the local invasive behavior of primary tumors (Wu and Lin 2014).…”

Section: Disrupting the Gradientmentioning

confidence: 99%

Physical and Chemical Gradients in the Tumor Microenvironment Regulate Tumor Cell Invasion, Migration, and Metastasis

Oudin

Weaver

2016

Cold Spring Harb Symp Quant Biol

158

121

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Cancer metastasis requires the invasion of tumor cells into the stroma and the directed migration of tumor cells through the stroma toward the vasculature and lymphatics where they can disseminate and colonize secondary organs. Physical and biochemical gradients that form within the primary tumor tissue promote tumor cell invasion and drive persistent migration toward blood vessels and the lymphatics to facilitate tumor cell dissemination. These microenvironment cues include hypoxia and pH gradients, gradients of soluble cues that induce chemotaxis, and ions that facilitate galvanotaxis, as well as modifications to the concentration, organization, and stiffness of the extracellular matrix that produce haptotactic, alignotactic, and durotactic gradients. These gradients form through dynamic interactions between the tumor cells and the resident fibroblasts, adipocytes, nerves, endothelial cells, infiltrating immune cells, and mesenchymal stem cells. Malignant progression results from the integrated response of the tumor to these extrinsic physical and chemical cues. Here, we first describe how these physical and chemical gradients develop, and we discuss their role in tumor progression. We then review assays to study these gradients. We conclude with a discussion of clinical strategies used to detect and inhibit these gradients in tumors and of new intervention opportunities. Clarifying the role of these gradients in tumor evolution offers a unique approach to target metastasis.Tumors are highly heterogeneous and this feature compromises treatment efficacy and promotes tumor cell dissemination and metastasis to reduce patient survival. Tumor heterogeneity is driven in part by genetic alterations induced through genomic instability and maintained by the evolutionary selection of these genetically modified cells (Alizadeh et al. 2015). Epigenetic, transcriptional, and posttranslational modifications also contribute significantly to tumor cell diversity. Furthermore, cancer develops within a complex tissue microenvironment that itself fosters tumor heterogeneity through clonal selection as well as via epigenetic reprogramming and modifications of the tumor phenotype. The tumor microenvironment is composed of cellular constituents that include cells of the vasculature, infiltrating immune cells, and resident fibroblasts, adipocytes and nerves, and a noncellular component composed of diverse soluble factors and a highly variable and evolving insoluble extracellular matrix (ECM) (Joyce and Pollard 2009). The composition and organization of the tumor microenvironment vary significantly within and across tumors.One key feature of the noncellular microenvironment is the existence of local chemical and physical gradients that exert profound effects on the tumor phenotype, including its predilection to disseminate. In this regard, metastasis is facilitated by efficient local tumor cell invasion that is fostered by ECM and chemokine/cytokine/growth factor gradients which cooperate to promote the directional migration of the t...

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“…For this purpose we constructed a unique experimental model–two sublines of Walker carcinosarcoma WC256 cells representing: (i) mesenchymal migration, characterized by strong adhesion and formation of lamellipodia (LC) and (ii) ameboid migration, characterized by weak adhesion and formation of blebs (BC). As both cell sublines were adherent, they were suitable for use in 2D electrotactic chambers [ 44 ]. Bleb formation in BC cells was clearly visible under light and scanning electron microscope.…”

Section: Discussionmentioning

confidence: 99%

Lamellipodia and Membrane Blebs Drive Efficient Electrotactic Migration of Rat Walker Carcinosarcoma Cells WC 256

et al. 2016

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The endogenous electric field (EF) may provide an important signal for directional cell migration during wound healing, embryonic development and cancer metastasis but the mechanism of cell electrotaxis is poorly understood. Additionally, there is no research addressing the question on the difference in electrotactic motility of cells representing various strategies of cell movement—specifically blebbing vs. lamellipodial migration. In the current study we constructed a unique experimental model which allowed for the investigation of electrotactic movement of cells of the same origin but representing different modes of cell migration: weakly adherent, spontaneously blebbing (BC) and lamellipodia forming (LC) WC256 cells. We report that both BC and LC sublines show robust cathodal migration in a physiological EF (1–3 V/cm). The directionality of cell movement was completely reversible upon reversing the field polarity. However, the full reversal of cell direction after the change of EF polarity was much faster in the case of BC (10 minutes) than LC cells (30 minutes). We also investigated the distinct requirements for Rac, Cdc42 and Rho pathways and intracellular Ca2+ in electrotaxis of WC256 sublines forming different types of cell protrusions. It was found that Rac1 is required for directional movement of LC to a much greater extent than for BC, but Cdc42 and RhoA are more crucial for BC than for LC cells. The inhibition of ROCK did not affect electrotaxis of LC in contrast to BC cells. The results also showed that intracellular Ca2+ is essential only for the electrotactic reaction of BC cells. Moreover, inhibition of MLCK and myosin II did not affect the electrotaxis of LC in contrast to BC cells. In conclusion, our results revealed that both lamellipodia and membrane blebs can efficiently drive electrotactic migration of WC 256 carcinosarcoma cells, however directional migration is mediated by different signalling pathways.

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Recent Developments in Electrotaxis Assays

Cited by 14 publications

References 28 publications

Collective cell migration: guidance principles and hierarchies

Collective cell migration: guidance principles and hierarchies

Physical and Chemical Gradients in the Tumor Microenvironment Regulate Tumor Cell Invasion, Migration, and Metastasis

Lamellipodia and Membrane Blebs Drive Efficient Electrotactic Migration of Rat Walker Carcinosarcoma Cells WC 256

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