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Bioelectric Control of Metastasis in Solid Tumors
Samantha L Payne1, Michael Levin2, Madeleine J Oudin1
1Department of Biomedical Engineering, Tufts University, Medford, Massachusetts.
Abstract:
As the leading cause of death in cancer, there is an urgent need to develop treatments to target the dissemination of primary tumor cells to secondary organs, known as metastasis. Bioelectric signaling has emerged in the last century as an important controller of cell growth, and with the development of current molecular tools we are now beginning to identify its role in driving cell migration and metastasis in a variety of cancer types. This review summarizes the currently available research for bioelectric signaling in solid tumor metastasis. We review the steps of metastasis and discuss how these can be controlled by bioelectric cues at the level of a cell, a population of cells, and the tissue. The role of ion channel, pump, and exchanger activity and ion flux is discussed, along with the importance of the membrane potential and the relationship between ion flux and membrane potential. We also provide an overview of the evidence for control of metastasis by external electric fields (EFs) and draw from examples in embryogenesis and regeneration to discuss the implications for endogenous EFs. By increasing our understanding of the dynamic properties of bioelectric signaling, we can develop new strategies that target metastasis to be translated into the clinic.
Insights
Bioelectric signaling controls cancer cell metastasis. Understanding ion channel activity and membrane potential offers new therapeutic targets to combat cancer spread and improve patient outcomes.
Area of Science:
- Oncology
- Cell Biology
- Biophysics
Background:
- Metastasis is the leading cause of cancer mortality, necessitating novel therapeutic strategies.
- Bioelectric signaling, involving cell membrane potential and ion flux, is increasingly recognized for its role in cancer progression.
- Molecular tools now allow investigation into bioelectric control of cell migration and metastasis.
Purpose of the Study:
- To review current research on bioelectric signaling in solid tumor metastasis.
- To discuss how bioelectric cues influence metastatic processes at cellular, population, and tissue levels.
- To explore the therapeutic potential of targeting bioelectric signaling for cancer treatment.
Main Methods:
- Literature review of existing research on bioelectric signaling and cancer metastasis.
- Analysis of the roles of ion channels, pumps, exchangers, and membrane potential in metastasis.
- Examination of evidence for external electric field (EF) control of metastasis, drawing parallels with embryogenesis and regeneration.
Main Results:
- Bioelectric signaling, through ion flux and membrane potential, significantly influences cancer cell migration and metastasis.
- Specific ion channel activities and membrane potential dynamics are implicated in controlling metastatic steps.
- External electric fields (EFs) demonstrate a role in metastasis, with implications for endogenous EFs.
Conclusions:
- A deeper understanding of bioelectric signaling dynamics is crucial for developing anti-metastasis strategies.
- Targeting bioelectric cues presents a promising avenue for novel cancer therapies.
- Translating insights into clinical applications could significantly impact cancer patient outcomes.
