dc.contributor.author
Beyer, Katharina
dc.contributor.author
Partecke, Lars Ivo
dc.contributor.author
Roetz, Felicitas
dc.contributor.author
Fluhr, Herbert
dc.contributor.author
Weiss, Frank Ulrich
dc.contributor.author
Heidecke, Claus-Dieter
dc.contributor.author
von Bernstorff, Wolfram
dc.date.accessioned
2018-06-08T10:25:59Z
dc.date.available
2017-06-26T10:34:33.808Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/20429
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-23732
dc.description.abstract
Background Though TRAIL has been hailed as a promising drug for tumour
treatment, it has been observed that many tumour cells have developed escape
mechanisms against TRAIL-induced apoptosis. As a receptor of LPS, TLR 4, which
is expressed on a variety of cancer cells, can be associated with TRAIL-
resistance of tumour cells and tumour progression as well as with the
generation of an anti-tumour immune response. Methods In this study, the
sensitivity to TRAIL-induced apoptosis as well as the influence of LPS-co-
stimulation on the cell viability of the pancreatic cancer cell lines PANC-1,
BxPC-3 and COLO 357 was examined by FACS analyses and a cell viability assay.
Subsequently, the expression of TRAIL-receptors was detected via FACS
analyses. Levels of osteoprotegerin (OPG) were also determined using an
enzyme-linked immunosorbent assay. Results PANC-1 cells were shown to be
resistant to TRAIL-induced apoptosis. This was accompanied by significantly
increased osteoprotegerin levels and a significantly decreased expression of
DR4. In contrast, TRAIL significantly induced apoptosis in COLO 357 cells and
to a lesser degree in BxPC-3 cells. Co-stimulation of COLO 357 as well as
BxPC-3 cells combining TRAIL and LPS resulted in a significant decrease in
TRAIL-induced apoptosis. In COLO 357 cells TRAIL-stimulation decreased the
levels of OPG thereby not altering the expression of the TRAIL-receptors 1–4
resulting in a high susceptibility to TRAIL-induced apoptosis. Co-stimulation
with LPS and TRAIL completely reversed the effect of TRAIL on OPG levels
reaching a 2-fold increase beyond the level of non-stimulated cells resulting
in a lower susceptibility to apoptosis. In BxPC-3, TRAIL stimulation decreased
the expression of DR4 and significantly increased the decoy receptors TRAIL-R3
and TRAIL-R4 leading to a decrease in TRAIL-induced apoptosis. OPG levels
remained unchanged. Co-stimulation with TRAIL and LPS further enhanced the
changes in TRAIL-receptor-expression promoting apoptosis resistance.
Conclusions Here it has been shown that TRAIL-resistance in pancreatic cancer
cells can be mediated by the inflammatory molecule LPS as well as by different
expression patterns of functional and non-functional TRAIL-receptors.
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Pancreas cancer
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
dc.title
LPS promotes resistance to TRAIL-induced apoptosis in pancreatic cancer
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Infectious Agents and Cancer. - 12 (2017), Artikel Nr. 30
dcterms.bibliographicCitation.doi
10.1186/s13027-017-0139-4
dcterms.bibliographicCitation.url
http://infectagentscancer.biomedcentral.com/articles/10.1186/s13027-017-0139-4
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000027247
refubium.note.author
Der Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000008366
dcterms.accessRights.openaire
open access