dc.contributor.author
Braunholz, Diana
dc.contributor.author
Saki, Mohammad
dc.contributor.author
Niehr, Franziska
dc.contributor.author
Oeztuerk, Merve
dc.contributor.author
Puertolas, Berta Borras
dc.contributor.author
Konschak, Rober
dc.contributor.author
Budach, Volker
dc.contributor.author
Tinhofer, Ingeborg
dc.date.accessioned
2018-06-08T04:18:32Z
dc.date.available
2016-11-03T11:53:16.958Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/17006
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-21186
dc.description.abstract
In solid tumours millions of cells are shed into the blood circulation each
day. Only a subset of these circulating tumour cells (CTCs) survive, many of
them presumable because of their potential to form multi-cellular clusters
also named spheroids. Tumour cells within these spheroids are protected from
anoikis, which allows them to metastasize to distant organs or re-seed at the
primary site. We used spheroid cultures of head and neck squamous cell
carcinoma (HNSCC) cell lines as a model for such CTC clusters for determining
the role of the epidermal growth factor receptor (EGFR) in cluster formation
ability and cell survival after detachment from the extra-cellular matrix. The
HNSCC cell lines FaDu, SCC-9 and UT-SCC-9 (UT-SCC-9P) as well as its cetuximab
(CTX)-resistant sub-clone (UT-SCC-9R) were forced to grow in an anchorage-
independent manner by coating culture dishes with the anti-adhesive polymer
poly-2-hydroxyethylmethacrylate (poly-HEMA). The extent of apoptosis,
clonogenic survival and EGFR signalling under such culture conditions was
evaluated. The potential of spheroid formation in suspension culture was found
to be positively correlated with the proliferation rate of HNSCC cell lines as
well as their basal EGFR expression levels. CTX and gefitinib blocked, whereas
the addition of EGFR ligands promoted anchorage-independent cell survival and
spheroid formation. Increased spheroid formation and growth were associated
with persistent activation of EGFR and its downstream signalling component
(MAPK/ERK). Importantly, HNSCC cells derived from spheroid cultures retained
their clonogenic potential in the absence of cell-matrix contact. Addition of
CTX under these conditions strongly inhibited colony formation in CTX-
sensitive cell lines but not their resistant subclones. Altogether, EGFR
activation was identified as crucial factor for anchorage-independent survival
of HNSCC cells. Targeting EGFR in CTC cluster formation might represent an
attractive anti-metastatic treatment approach in HNSCC.
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
dc.title
Spheroid Culture of Head and Neck Cancer Cells Reveals an Important Role of
EGFR Signalling in Anchorage Independent Survival
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
PLoS ONE. - 11 (2016), 9, Artikel Nr. e0163149
dcterms.bibliographicCitation.doi
10.1371/journal.pone.0163149
dcterms.bibliographicCitation.url
http://dx.doi.org/10.1371/journal.pone.0163149
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000025656
refubium.note.author
Der Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000007302
dcterms.accessRights.openaire
open access