Accruing evidence indicates that exposure to environmental compounds may adversely affect human health and promote carcinogenesis. Triclosan (TCS), an antimicrobial agent widely used as a preservative in personal care products, has been shown to act as an endocrine disruptor in hormone-dependent tissues. Here, we demonstrate a new molecular mechanism by which TCS stimulates the secretion by human prostate cancer stromal cells of vascular endothelial growth factor (VEGF), a factor known to promote tumor growth. This mechanism involves an increase in intracellular calcium levels due to the direct activation of a membrane ion channel. Using calcium imaging and electrophysiology techniques, we show for the first time that environmentally relevant concentrations of TCS activate a cation channel of the TRP family, TRPA1 (Transient Receptor Potential Ankirin 1), in primary cultured human prostate cancer stromal cells. The TCS-induced TRPA1 activation increased basal calcium in stromal cells and stimulated the secretion of VEGF and epithelial cells proliferation. Interestingly, immunofluorescence labeling performed on formalin-fixed paraffin-embedded prostate tissues showed an exclusive expression of the TRPA1 channel in prostate cancer stromal cells. Our data demonstrate an impact of the environmental factor TCS on the tumor microenvironment interactions, by activating a tumor stroma-specific TRPA1 ion channel. Cancer Prev Res; 10(3); 177–87. ©2017 AACR.
Note: Supplementary data for this article are available at Cancer Prevention Research Online (http://cancerprevres.aacrjournals.org/).
- Received October 11, 2016.
- Revision received December 30, 2016.
- Accepted January 3, 2017.
- ©2017 American Association for Cancer Research.