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Effects of physiological electric fields on migration of human dermal fibroblasts.

ABSTRACT: Endogenous electric currents generated instantly at skin wounds direct migration of epithelial cells and are likely to be important in wound healing. Migration of fibroblasts is critical in wound healing. It remains unclear how wound electric fields guide migration of dermal fibroblasts. We report here that mouse skin wounds generated endogenous electric currents for many hours. Human dermal fibroblasts of both primary and cell-line cultures migrated directionally but slowly toward the anode in an electric field of 50-100 mV mm(-1). This is different from keratinocytes, which migrate quickly to the cathode. It took more than 1 hour for dermal fibroblasts to manifest detectable directional migration. Larger field strength (400 mV mm(-1)) was required to induce directional migration within 1 hour after onset of the field. Phosphatidylinositol-3-OH kinase (PI3 kinase) mediates cathode-directed migration of keratinocytes. We tested the role of PI3 kinase in anode-directed migration of fibroblasts. An applied electric field activated PI3 kinase/Akt in dermal fibroblasts. Dermal fibroblasts from p110gamma (a PI3 kinase catalytic subunit) null mice showed significantly decreased directional migration. These results suggest that physiological electric fields may regulate motility of dermal fibroblasts and keratinocytes differently, albeit using similar PI3 kinase-dependent mechanisms.

SUBMITTER: Guo A

PROVIDER: S-EPMC2952177 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Effects of physiological electric fields on migration of human dermal fibroblasts.

Guo Aihua A Song Bing B Reid Brian B Gu Yu Y Forrester John V JV Jahoda Colin A B CA Zhao Min M

The Journal of investigative dermatology 20100422 9

Endogenous electric currents generated instantly at skin wounds direct migration of epithelial cells and are likely to be important in wound healing. Migration of fibroblasts is critical in wound healing. It remains unclear how wound electric fields guide migration of dermal fibroblasts. We report here that mouse skin wounds generated endogenous electric currents for many hours. Human dermal fibroblasts of both primary and cell-line cultures migrated directionally but slowly toward the anode in ...[more]

PMID: 20410911

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Project description:Glioblastoma multiforme (GBM), is the most common form of adult malignant brain tumor, highly heterogeneous and relatively resistant to therapy with a poor prognosis. As other cancers, GBM starts from a relatively small fraction of poorly differentiated and particularly aggressive cancer stem cells (CSCs), responsible for aberrant proliferation and invasion, rapidly spreading the tumor growth in the other parts of the central nervous system. Due to the extreme tumor heterogeneity, standard therapies (i.e., surgery, chemotherapy and radiotherapy) provide poor positive outcomes and cancers usually recur. Therefore, alternative approaches, possibly targeting CSCs, are necessary for searching effective therapeutic strategies against GBM. Among many emerging new therapeutic strategies, ultra-short pulsed electric fields (PEF) are considered extremely promising in cancer therapy and our previous results demonstrated the capability of a specific electric pulse protocol, characterized by a high pulse amplitude and a short duration, to selectively affect medulloblastoma CSCs preserving normal cells. Here, we tested the same exposure protocol to investigate the response of U87 GBM cells, and of U87-derived neurospheres. By analyzing different in vitro biological endpoints and taking advantage of transcriptomic and bioinformatics analyses, we found that, independently of CSCs content, PEF exposure affected cell proliferation and differentially regulated hypoxia, inflammation and P53/cell cycle checkpoints. PEF exposure also significantly reduced the clonogenic potential, reducing the ability to form new neurospheres, and inhibited the invasion potential. Importantly, exclusively in U87 neurospheres, PEF exposure changed the expression of stemness/differentiation genes. Our results, confirm this physical stimulus as a promising treatment to destabilize the extreme intra-tumoral GBM heterogeneity opening up the possibility to develop future therapeutic strategies mediated by PEF exposure.

Dataset Information

Effects of physiological electric fields on migration of human dermal fibroblasts.

Publications

Effects of physiological electric fields on migration of human dermal fibroblasts.

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