title: Activation of TRPA1 Channel by Antibacterial Agent Triclosan Induces VEGF Secretion in Human Prostate Cancer Stromal Cells.
abstract: 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.
authors.affiliation: Univ. Lille, Inserm, U1003 - PHYCEL - Physiologie Cellulaire, F-59000 Lille, Equipe labellisée par la Ligue Nationale contre le cancer, Villeneuve d'Ascq, France; Laboratory of Excellence, Ion Channels Science and Therapeutics; Université Lille I Sciences et Technologies, Villeneuve d'Ascq, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Derouiche
authors.affiliation: Univ. Lille, Inserm, U1003 - PHYCEL - Physiologie Cellulaire, F-59000 Lille, Equipe labellisée par la Ligue Nationale contre le cancer, Villeneuve d'Ascq, France; Laboratory of Excellence, Ion Channels Science and Therapeutics; Université Lille I Sciences et Technologies, Villeneuve d'Ascq, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Mariot
authors.affiliation: Univ. Lille, Inserm, U1003 - PHYCEL - Physiologie Cellulaire, F-59000 Lille, Equipe labellisée par la Ligue Nationale contre le cancer, Villeneuve d'Ascq, France; Laboratory of Excellence, Ion Channels Science and Therapeutics; Université Lille I Sciences et Technologies, Villeneuve d'Ascq, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Warnier
authors.affiliation: Univ. Lille, Inserm, U1003 - PHYCEL - Physiologie Cellulaire, F-59000 Lille, Equipe labellisée par la Ligue Nationale contre le cancer, Villeneuve d'Ascq, France; Laboratory of Excellence, Ion Channels Science and Therapeutics; Université Lille I Sciences et Technologies, Villeneuve d'Ascq, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Vancauwenberghe
authors.affiliation: Univ. Lille, Inserm, U1003 - PHYCEL - Physiologie Cellulaire, F-59000 Lille, Equipe labellisée par la Ligue Nationale contre le cancer, Villeneuve d'Ascq, France; Laboratory of Excellence, Ion Channels Science and Therapeutics; Université Lille I Sciences et Technologies, Villeneuve d'Ascq, France.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bidaux
authors.affiliation: Département de Pathologies, Laboratoire d'Anatomie et de Cytologie Pathologique, Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), Lille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Gosset
authors.affiliation: Univ. Lille, Inserm, U1003 - PHYCEL - Physiologie Cellulaire, F-59000 Lille, Equipe labellisée par la Ligue Nationale contre le cancer, Villeneuve d'Ascq, France; Laboratory of Excellence, Ion Channels Science and Therapeutics; Université Lille I Sciences et Technologies, Villeneuve d'Ascq, France.|Service d'Urologie de l'hôpital St-Philibert, Lomme, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Mauroy
authors.affiliation: Univ. Lille, Inserm, U1003 - PHYCEL - Physiologie Cellulaire, F-59000 Lille, Equipe labellisée par la Ligue Nationale contre le cancer, Villeneuve d'Ascq, France; Laboratory of Excellence, Ion Channels Science and Therapeutics; Université Lille I Sciences et Technologies, Villeneuve d'Ascq, France.|Service d'Urologie de l'hôpital St-Philibert, Lomme, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Bonnal
authors.affiliation: Univ. Lille, Inserm, U1003 - PHYCEL - Physiologie Cellulaire, F-59000 Lille, Equipe labellisée par la Ligue Nationale contre le cancer, Villeneuve d'Ascq, France; Laboratory of Excellence, Ion Channels Science and Therapeutics; Université Lille I Sciences et Technologies, Villeneuve d'Ascq, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Slomianny
authors.affiliation: Univ. Lille, Inserm, U1003 - PHYCEL - Physiologie Cellulaire, F-59000 Lille, Equipe labellisée par la Ligue Nationale contre le cancer, Villeneuve d'Ascq, France; Laboratory of Excellence, Ion Channels Science and Therapeutics; Université Lille I Sciences et Technologies, Villeneuve d'Ascq, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Delcourt
authors.affiliation: Univ. Lille, Inserm, U1003 - PHYCEL - Physiologie Cellulaire, F-59000 Lille, Equipe labellisée par la Ligue Nationale contre le cancer, Villeneuve d'Ascq, France; Laboratory of Excellence, Ion Channels Science and Therapeutics; Université Lille I Sciences et Technologies, Villeneuve d'Ascq, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Dewailly
authors.affiliation: Univ. Lille, Inserm, U1003 - PHYCEL - Physiologie Cellulaire, F-59000 Lille, Equipe labellisée par la Ligue Nationale contre le cancer, Villeneuve d'Ascq, France; Laboratory of Excellence, Ion Channels Science and Therapeutics; Université Lille I Sciences et Technologies, Villeneuve d'Ascq, France.
authors.forename: Natalia
authors.initials: N
authors.lastname: Prevarskaya
authors.affiliation: Univ. Lille, Inserm, U1003 - PHYCEL - Physiologie Cellulaire, F-59000 Lille, Equipe labellisée par la Ligue Nationale contre le cancer, Villeneuve d'Ascq, France; Laboratory of Excellence, Ion Channels Science and Therapeutics; Université Lille I Sciences et Technologies, Villeneuve d'Ascq, France. morad.roudbaraki@univ-lille1.fr.
authors.forename: Morad
authors.initials: M
authors.lastname: Roudbaraki
mesh_terms: D000891:Anti-Infective Agents, Local / Q000633:toxicity*; D015220:Calcium Channels / Q000378:metabolism*; D002274:Carcinogens, Environmental / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000378:metabolism*; D014260:Triclosan / Q000633:toxicity*; D059016:Tumor Microenvironment / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D000891:Anti-Infective Agents, Local; D015220:Calcium Channels; D002274:Carcinogens, Environmental; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014260:Triclosan