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Statements

Subject Item
n2:RIV%2F61989592%3A15310%2F13%3A33148029%21RIV14-MSM-15310___
rdf:type
skos:Concept n11:Vysledek
rdfs:seeAlso
http://link.springer.com/article/10.1007%2Fs00204-013-1045-1
dcterms:description
Metastases destroy the function of infested organs and are the main reason of cancer-related mortality. Heteronemin, a natural product derived from a marine sponge, was tested in vitro regarding its properties to prevent tumour cell intravasation through the lymph-endothelial barrier. In three-dimensional (3D) cell cultures consisting of MCF-7 breast cancer cell spheroids that were placed on lymph-endothelial cell (LEC) monolayers, tumour cell spheroids induce %22circular chemorepellent-induced defects%22 (CCIDs) in the LEC monolayer; 12(S)-Hydroxyeicosatetraenoic acid (12(S)-HETE) and NF-kappa B activity are major factors inducing CCIDs, which are entry gates for tumour emboli intravasating the vasculature. This 3D co-culture is a validated model for the investigation of intravasation mechanisms and of drugs preventing CCID formation and hence lymph node metastasis. Furthermore, Western blot analyses, NF-kappa B reporter, EROD, SELE, 12(S)-HETE, and adhesion assays were performed to investigate the properties of heteronemin. Five micromolar heteronemin inhibited the directional movement of LECs and, therefore, the formation of CCIDs, which were induced by MCF-7 spheroids. Furthermore, heteronemin reduced the adhesion of MCF-7 cells to LECs and suppressed 12(S)-HETE-induced expression of the EMT marker paxillin, which is a regulator of directional cell migration. The activity of CYP1A1, which contributed to CCID formation, was also inhibited by heteronemin. Hence, heteronemin inhibits important mechanisms contributing to tumour intravasation in vitro and should be tested in vivo. Metastases destroy the function of infested organs and are the main reason of cancer-related mortality. Heteronemin, a natural product derived from a marine sponge, was tested in vitro regarding its properties to prevent tumour cell intravasation through the lymph-endothelial barrier. In three-dimensional (3D) cell cultures consisting of MCF-7 breast cancer cell spheroids that were placed on lymph-endothelial cell (LEC) monolayers, tumour cell spheroids induce %22circular chemorepellent-induced defects%22 (CCIDs) in the LEC monolayer; 12(S)-Hydroxyeicosatetraenoic acid (12(S)-HETE) and NF-kappa B activity are major factors inducing CCIDs, which are entry gates for tumour emboli intravasating the vasculature. This 3D co-culture is a validated model for the investigation of intravasation mechanisms and of drugs preventing CCID formation and hence lymph node metastasis. Furthermore, Western blot analyses, NF-kappa B reporter, EROD, SELE, 12(S)-HETE, and adhesion assays were performed to investigate the properties of heteronemin. Five micromolar heteronemin inhibited the directional movement of LECs and, therefore, the formation of CCIDs, which were induced by MCF-7 spheroids. Furthermore, heteronemin reduced the adhesion of MCF-7 cells to LECs and suppressed 12(S)-HETE-induced expression of the EMT marker paxillin, which is a regulator of directional cell migration. The activity of CYP1A1, which contributed to CCID formation, was also inhibited by heteronemin. Hence, heteronemin inhibits important mechanisms contributing to tumour intravasation in vitro and should be tested in vivo.
dcterms:title
In vitro characterisation of the anti-intravasative properties of the marine product heteronemin In vitro characterisation of the anti-intravasative properties of the marine product heteronemin
skos:prefLabel
In vitro characterisation of the anti-intravasative properties of the marine product heteronemin In vitro characterisation of the anti-intravasative properties of the marine product heteronemin
skos:notation
RIV/61989592:15310/13:33148029!RIV14-MSM-15310___
n11:predkladatel
n12:orjk%3A15310
n3:aktivita
n20:P
n3:aktivity
P(ED0007/01/01)
n3:cisloPeriodika
10
n3:dodaniDat
n7:2014
n3:domaciTvurceVysledku
n13:6086187 n13:4712048
n3:druhVysledku
n4:J
n3:duvernostUdaju
n10:S
n3:entitaPredkladatele
n17:predkladatel
n3:idSjednocenehoVysledku
79399
n3:idVysledku
RIV/61989592:15310/13:33148029
n3:jazykVysledku
n15:eng
n3:klicovaSlova
Mobility; Adhesion; Lymph endothelium; Intravasation; Heteronemin
n3:klicoveSlovo
n8:Adhesion n8:Heteronemin n8:Lymph%20endothelium n8:Intravasation n8:Mobility
n3:kodStatuVydavatele
DE - Spolková republika Německo
n3:kontrolniKodProRIV
[8D7B099DB11D]
n3:nazevZdroje
Archives of Toxicology
n3:obor
n19:ED
n3:pocetDomacichTvurcuVysledku
2
n3:pocetTvurcuVysledku
24
n3:projekt
n21:ED0007%2F01%2F01
n3:rokUplatneniVysledku
n7:2013
n3:svazekPeriodika
87
n3:tvurceVysledku
Kopf, Sabine Jarukamjorn, Kanokwan De Martin, Rainer Viola, Katharina Raab, Ingrid Vonach, Caroline Krieger, Sigurd Giessrigl, Benedikt Dolznig, Helmut Teichmann, Mathias Huttary, Nicole Atanasov, Atanas G Dirsch, Verena M Rárová, Lucie Strnad, Miroslav Kretschy, Nicole Grusch, Michael Schumacher, Marc Krupitza, Georg Diederich, Marc Szekeres, Thomas Mikulits, Wolfgang Jäger, Walter Saiko, Philipp
n3:wos
000324773300008
s:issn
0340-5761
s:numberOfPages
11
n5:doi
10.1007/s00204-013-1045-1
n14:organizacniJednotka
15310