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Updated: Aug 29, 2026
Utilizing Custom-designed Galvanotaxis Chambers to Study Directional Migration of Prostate Cells
Published on: December 7, 2014
Voltage-gated Na+ channels confer invasive properties on human prostate cancer cells
Eric S Bennett1, Beth A Smith, Jean M Harper
1Department of Physiology and Biophysics, Program in Neuroscience, University of South Florida College of Medicine MDC 8, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA. esbennet@hsc.usf.edu
Abstract:
Prostate cancer is the second leading cause of cancer deaths in American males, resulting in an estimated 37,000 deaths annually, typically the result of metastatic disease. A consequence of the unsuccessful androgen ablation therapy used initially to treat metastatic disease is the emergence of androgen-insensitive prostate cancer, for which there is currently no prescribed therapy. Here, three related human prostate cancer cell lines that serve as a model for this dominant form of prostate cancer metastasis were studied to determine the correlation between voltage-gated sodium channel expression/function and prostate cancer metastatic (invasive) potential: the non-metastatic, androgen-dependent LNCaP LC cell line and two increasingly tumorogenic, androgen-independent daughter cell lines, C4 and C4-2. Fluorometric in vitro invasion assays indicated that C4 and C4-2 cells are more invasive than LC cells. Immunoblot analysis showed that voltage-gated sodium channel expression increases with the invasive potential of the cell line, and this increased invasive potential can be blocked by treatment with the specific voltage-gated sodium channel inhibitor, tetrodotoxin (TTX). These data indicate that increased voltage-gated sodium channel expression and function are necessary for the increased invasive potential of these human prostate cancer cells. When the human adult skeletal muscle sodium channel Na(v1.4) was expressed transiently in each cell line, there was a highly significant increase in the numbers of invading LC, C4, and C4-2 cells. This increased invasive potential was reduced to control levels by treatment with TTX. These data are the first to indicate that the expression of voltage-gated sodium channels alone is sufficient to increase the invasive potential of non-metastatic (LC cells) as well as more aggressive cells (i.e., C4 and C4-2 cells). Together, the data suggest that increased voltage-gated sodium channel expression alone is necessary and sufficient to increase the invasive potential of a set of human prostate cancer cell lines that serve as a model for prostate cancer metastasis.
Insights
Increased voltage-gated sodium channel expression drives prostate cancer metastasis. Blocking these channels with tetrodotoxin (TTX) reduces cancer cell invasion, indicating their crucial role in aggressive disease progression.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Prostate cancer metastasis is a leading cause of death in men.
- Androgen-insensitive prostate cancer lacks effective therapies.
- Voltage-gated sodium channels (VGSCs) are implicated in cancer progression.
Purpose of the Study:
- To investigate the correlation between VGSC expression/function and prostate cancer metastatic potential.
- To determine if VGSC activity is necessary and/or sufficient for prostate cancer cell invasion.
Main Methods:
- Utilized three human prostate cancer cell lines (LNCaP LC, C4, C4-2) modeling metastasis.
- Performed fluorometric in vitro invasion assays.
- Conducted immunoblot analysis for VGSC expression.
- Administered tetrodotoxin (TTX) to inhibit VGSCs.
- Transiently expressed Na(v)1.4 sodium channel in cell lines.
Main Results:
- Invasive potential increased with VGSC expression across cell lines.
- VGSC inhibition with TTX significantly reduced cancer cell invasion.
- Expression of Na(v)1.4 alone increased invasive potential in all cell lines.
- TTX treatment reversed the Na(v)1.4-induced increase in invasion.
Conclusions:
- Increased VGSC expression and function are necessary for prostate cancer cell invasion.
- VGSC expression alone is sufficient to enhance the invasive potential of prostate cancer cells.
- Targeting VGSCs may offer a therapeutic strategy for metastatic prostate cancer.
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