How Gaps Between Cells Can Help Fight Cancer
A new study shows that gaps between cells can be the next tool to fight cancer development due to electricity properties.
Author: Iris Gutierrez
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Neuroanatomy
Introduction
The current cancer treatments available may not work for all types or severities of cancer and new treatments must be created and tested. However, first the mechanisms of cancer and tumor development and its precursors must be understood. There is quite a bit of current research available to understand that cancer can develop, form, and look differently between individuals but that is exactly why it is hard to treat. New research has been found that looks at how the gaps between cells (gap junctions) may play a key role in future cancer treatment. In a study published in the Journal Developmental Neurobiology, researchers investigate the connectivity, networks, and electrical properties of these gap junctions. The researchers found that healthy tissue has a higher number of gap junction cells compared to tumorous tissues and that isolation of these gap junctions leads to a promotion of tumor development1. It was also found that the electricity produced by our cells can also help further regulate cell processes6,9, development, and restoration after injury7,8, but can also be used to change cancerous cells into normal cells2,9. This discovery is an important step forward because it begins to associate gap junctions as communication centers, and how these junctions are used to control cell growth2,9. This not only provides us with some insight about gap junctions, but also signals hope for a new possible cancer treatment.
Background
Gap junctions are characterized as channels that help directly connect cells together. These gap junctions are made out of two major proteins, the connexin and innexin proteins, which aid in the transfer of molecules from one cell to another1. These cells differ from neuron cell gaps (synapses) because gap junctions are able to form complex connections that would not be possible for transmitting chemical signals1. These chemical signals as well as the electrical aspects of this article are mainly referring to the flow of charged ions between cells or between the inside and the outside of the cell4. The normal charge inside of our cells when the cell is not being activated (the resting membrane potential) is typically a negative charge, compared to the positive charge exhibited by the outside of the cell4.
Additionally, current cancer research shows that there’s primarily 3 ways that cancer is caused; the first way is through genetic inheritance, the second is through environmental factors, and the last way is through random mutations3. This study mainly focuses on the random mutation and genetic inheritance aspects of cancer development.
Methods
The study was mainly conducted in a literature review fashion, where researchers reviewed the existing literature available on gap junctions, cancerous tumor development, bioelectricity, membrane potentiation and more. Other methodology included in vitro and in vivo comparisons of resting membrane potentials of healthy and cancerous breast tissue5, as well as regeneration of fins within zebrafish due to possible gap junction communication1.
Results
The researchers found a variety of different things, all pointing to the notion that these gap junctions are a major source of cell-to-cell communication because of the bioelectrical properties as well as its relationship with the cell’s membrane potential1,5. Gap junctions and the membrane potentials bidirectionally effect each other since gap junctions regulate the spread of the membrane potential between neighboring cells, and the membrane potential can regulate the gap junction opening1. As mentioned above, the membrane potential in healthy cells is typically more negatively charged within the cell versus the outside of the cell4,5. Interestingly, cancer cells and tumors are the opposite, since they are more positively charged inside versus the outside of the cell4,5. This positive (or more depolarized) charge within the cell is said to be a signal for cells to continue dividing and spreading1,4,5,9.
By changing the bioelectricity through ion channels at the gap junctions, it has been possible to change the positively charged cancer/tumor cells into negatively charged, healthy cells, while also reducing the number of new cancerous cells2,6,7,9. This change in bioelectricity not only helped to reverse cancer, but also can help to further regulate processes like cancer cell migration (for metastasis protection), epithelial wound repair, spinal cord repair and more6,9,10.
Conclusion
The results found give us a huge step forward in the future of cancer development, treatment, and even diagnosis. The detection of a cell or bundle of cells with a positive charge can fundamentally change the way cancer is detected and may even catch tumor formation at an earlier stage. Meanwhile, the manipulation of the membrane potential/bioelectricity by manipulating ion channels through cell gap junctions can aid and perhaps even reverse cancer! These results are an incredible feat, and more research needs to be done to figure out complete mechanisms for the technique in humans and then increase public accessibility of the new treatment. By uncovering the secret mechanisms of how cancer works will ultimately aid us in the fight against cancer, and lead to a better quality of life for all.
[+] References
Mathews, J., & Levin, M. (2017). Gap junctional signaling in pattern regulation: Physiological network connectivity instructs growth and form. Developmental Neurobiology, 77(5), 643-673. doi: http://ntserver1.wsulibs.wsu.edu:2099/10.1002/dneu.22405
Payne, S., Department of Biomedical Engineering and Tufts University, Levin, M., Center, A., Oudin, M., Phillips, J. (2019, September 16). Bioelectric Control of Metastasis in Solid Tumors. https://www.liebertpub.com/doi/10.1089/bioe.2019.0013
Pratt, C. W., & Cornely, K. (n.d.). Essential Biochemistry (4 ed.). Wiley. https://edugen.wileyplus.com/edugen/lti/main.uni
Tyler, S. (2017, August 11). Nature's electric potential: A systematic review of the role of Bioelectricity in wound healing and Regenerative processes in Animals, humans, and plants. https://www.frontiersin.org/articles/10.3389/fphys.2017.00627/full
Yang, M., & Brackenbury, W. (2013, June 28). Membrane potential and cancer progression. Retrieved April 29, 2021, from https://www.frontiersin.org/articles/10.3389/fphys.2013.00185/full
McCaig, C., Song, B., & Rajnicek, A. (2009, December 01). Electrical dimensions in cell science. https://journals.biologists.com/jcs/article/122/23/4267/30654/Electrical-dimensions-in-cell-science
McLaughlin, K., & Levin, M. (2017, December 25). Bioelectric signaling In Regeneration: Mechanisms of ionic controls of growth and form. https://www.sciencedirect.com/science/article/pii/S0012160617303846?via%3Dihub
Mathews, J., & Levin, M. (2018, April 21). The body electric 2.0: Recent advances in developmental Bioelectricity for regenerative and synthetic bioengineering. https://www.sciencedirect.com/science/article/pii/S0958166917302690?via%3Dihub#fig0025
Scishow (Hank Green). (2020, August 27). How the electricity in our bodies could fight cancer [Video file]. https://www.youtube.com/watch?v=U0C1rtDak40
Bugan, I., Kucuk, S., Karagoz, Z., Fraser, S., Kaya, H., Dodson, A., . . . Djamgoz, M. (2019, March 20). Anti-metastatic effect of ranolazine in an in vivo rat model of prostate cancer, and expression of voltage-gated sodium channel protein in human prostate. https://www.nature.com/articles/s41391-019-0128-3
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