Impact of Wnt signalling on CXCR4 expression and function

#3251

Introduction: Loss of Somatostatin Receptor 2 (SSTR2) expression and rising Chemokine Receptor Type 4 (CXCR4) expression are associated with increasing dedifferentiation in Neuroendocrine Tumors (NET). CXCR4 expression is associated with enhanced metastatic and invasive potential and worse prognosis in NET, but might be a theranostic target in NET not sufficiently expressing SSTR2. Likewise, aberrant activation of Wnt/β-catenin signalling may promote a more aggressive phenotype in NET.

Aim(s): We hypothesized an interaction of the Wnt/β-catenin pathway with CXCR4 expression and function in NET. Activation of Wnt signalling might lead to an increase in CXCR4 expression and function, while inhibition would have opposite effects.

Materials and methods: The NET cell lines BON-1 and QGP-1 were exposed to Wnt inhibitors (5-aza-CdR, Quercetine, Niclosamide) or the Wnt activator LiCl. The expression of Wnt pathway genes and of CXCR4 were studied by qRT-PCR, Western Blot and immunohistochemistry. Effects of Wnt modulators on the uptake of the CXCR4 ligand [68Ga] Pentixafor were measured.

Conference: 18th Annual ENETS Concerence (2021)

Presenting Author: Weich A

Authors: Weich A, Rogoll D, Mayer L, Meining A, Kudlich T,

Keywords: neuroendocrine, NET, CXCR4, Wnt, Wnt Signalling, beta-catenin, BON-1, QGP-1,