TY  - JOUR
A1  - Weich, Alexander
A1  - Rogoll, Dorothee
A1  - Gawlas, Sophia
A1  - Mayer, Lars
A1  - Weich, Wolfgang
A1  - Pongracz, Judit
A1  - Kudlich, Theodor
A1  - Meining, Alexander
A1  - Scheurlen, Michael
T1  - Wnt/β-catenin signaling regulates CXCR4 expression and [\(^{68}\)Ga] Pentixafor internalization in neuroendocrine tumor cells
JF  - Diagnostics
N2  - Loss of Somatostatin Receptor 2 (SSTR2) expression and rising CXC Chemokine Receptor Type 4 (CXCR4) expression are associated with dedifferentiation in neuroendocrine tumors (NET). In NET, CXCR4 expression is associated with enhanced metastatic and invasive potential and worse prognosis but might be a theragnostic target. Likewise, activation of Wnt/β-catenin signaling may promote a more aggressive phenotype in NET. We hypothesized an interaction of the Wnt/β-catenin pathway with CXCR4 expression and function in NET. The NET cell lines BON-1, QGP-1, and MS-18 were exposed to Wnt inhibitors (5-aza-CdR, quercetin, and niclosamide) or the Wnt activator LiCl. The expressions of Wnt pathway genes and of CXCR4 were studied by qRT-PCR, Western blot, and immunohistochemistry. The effects of Wnt modulators on uptake of the CXCR4 ligand [\(^{68}\)Ga] Pentixafor were measured. The Wnt activator LiCl induced upregulation of CXCR4 and Wnt target gene expression. Treatment with the Wnt inhibitors had opposite effects. LiCl significantly increased [\(^{68}\)Ga] Pentixafor uptake, while treatment with Wnt inhibitors decreased radiopeptide uptake. Wnt pathway modulation influences CXCR4 expression and function in NET cell lines. Wnt modulation might be a tool to enhance the efficacy of CXCR4-directed therapies in NET or to inhibit CXCR4-dependent proliferative signaling. The underlying mechanisms for the interaction of the Wnt pathway with CXCR4 expression and function have yet to be clarified.
KW  - neuroendocrine tumor
KW  - NET
KW  - Wnt
KW  - β-catenin
KW  - CXCR4
KW  - [\(^{68}\)Ga] Pentixafor
KW  - BON-1
KW  - QGP-1
KW  - MS-18
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228914
SN  - 2075-4418
VL  - 11
IS  - 2
ER  - 
TY  - JOUR
A1  - Rogoll, Dorothee
A1  - Schauber, Jürgen
A1  - Mheta, Koy K.
A1  - Stich, August
A1  - Scheppach, Wolfgang
T1  - Differential Cathelicidin Expression in Duodenal and Gastric Biopsies from Tanzanian and German Patients
JF  - PLoS One
N2  - Background
Epithelial surfaces such as the gastrointestinal mucosa depend on expression of antimicrobial peptides like cathelicidin for immune defence against pathogens. The mechanisms behind mucosal cathelicidin regulation are incompletely understood.

Methods
Cathelicidin expression was analysed in duodenal, antral and corpus/fundic mucosal biopsies from African and German patients. Additionally, cathelicidin expression was correlated with Helicobacter pylori (HP) infection and the inflammatory status of the mucosa.

Results
High cathelicidin transcript abundance was detected in duodenal biopsies from African subjects. On the contrary, cathelicidin mRNA expression was either undetectable or very low in tissue specimens from German patients. Also, in the antrum and corpus/fundus regions of the stomach significantly higher cathelicidin transcript levels were measured in Tanzanian compared to German patients. In gastric biopsies from African patients cathelicidin expression was increased in HP positive compared to HP negative subjects. Additionally, the inflammatory status measured by IL-8 expression correlated well with the HP infection status.

Conclusions
A higher duodenal and gastric cathelicidin expression in African (compared with European) individuals may be due to upregulation by antigenic stimulation and may confer a higher resistance against enteric infections.
KW  - messenger RNA
KW  - german people
KW  - gastrointestinal tract
KW  - gastrointestinal infections
KW  - africans
KW  - antimicrobials
KW  - biopsy
KW  - helicobacter pylori infection
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137970
VL  - 6
IS  - 7
ER  -