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  -