dc.contributor.author
Walcher, Lia
dc.contributor.author
Budde, Clara
dc.contributor.author
Böhm, Arina
dc.contributor.author
Reinach, Peter S.
dc.contributor.author
Dhandapani, Priyavathi
dc.contributor.author
Ljubojevic, Nina
dc.contributor.author
Schweiger, Markus W.
dc.contributor.author
von der Waydbrink, Henriette
dc.contributor.author
Reimers, Ilka
dc.contributor.author
Köhrle, Josef
dc.contributor.author
Mergler, Stefan
dc.date.accessioned
2019-04-02T11:44:22Z
dc.date.available
2019-04-02T11:44:22Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/24268
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-2040
dc.description.abstract
In human uveal melanoma (UM), tumor enlargement is associated with increases in aqueous humor vascular endothelial growth factor-A (VEGF-A) content that induce neovascularization. 3-Iodothyronamine (3-T1AM), an endogenous thyroid hormone metabolite, activates TRP melastatin 8 (TRPM8), which blunts TRP vanilloid 1 (TRPV1) activation by capsaicin (CAP) in human corneal, conjunctival epithelial cells, and stromal cells. We compare here the effects of TRPM8 activation on VEGF-induced transactivation of TRPV1 in an UM cell line (92.1) with those in normal primary porcine melanocytes (PM) since TRPM8 is upregulated in melanoma. Fluorescence Ca2+-imaging and planar patch-clamping characterized functional channel activities. CAP (20 μM) induced Ca2+ transients and increased whole-cell currents in both the UM cell line and PM whereas TRPM8 agonists, 100 μM menthol and 20 μM icilin, blunted such responses in the UM cells. VEGF (10 ng/ml) elicited Ca2+ transients and augmented whole-cell currents, which were blocked by capsazepine (CPZ; 20 μM) but not by a highly selective TRPM8 blocker, AMTB (20 μM). The VEGF-induced current increases were not augmented by CAP. Both 3-T1AM (1 μM) and menthol (100 μM) increased the whole-cell currents, whereas 20 μM AMTB blocked them. 3-T1AM exposure suppressed both VEGF-induced Ca2+ transients and increases in underlying whole-cell currents. Taken together, functional TRPM8 upregulation in UM 92.1 cells suggests that TRPM8 is a potential drug target for suppressing VEGF induced increases in neovascularization and UM tumor growth since TRPM8 activation blocked VEGF transactivation of TRPV1.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
weal melanoma
en
dc.subject
3-iodothyronamine
en
dc.subject
vascular endothelial growth factor
en
dc.subject
Intracellular Ca2+
en
dc.subject
transient receptor potential vanilloid 1 channel
en
dc.subject
transient receptor potential melastatin 8
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
TRPM8 activation via 3-iodothyronamine blunts VEGF-induced transactivation of TRPV1 in human uveal melanoma cells
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
1234
dcterms.bibliographicCitation.doi
10.3389/fphar.2018.01234
dcterms.bibliographicCitation.journaltitle
Frontiers in Pharmacology
dcterms.bibliographicCitation.originalpublishername
Frontiers Media S.A.
dcterms.bibliographicCitation.volume
9
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
30483120
dcterms.isPartOf.issn
1663-9812