Wnt/β-Catenin Signaling Regulates CXCR4 Expression and [68Ga] Pentixafor Internalization in Neuroendocrine Tumor Cells

Diagnostics

Michael Scheurlen¹  Sophia Gawlas¹  Alexander Weich¹  Alexander Meining¹  Wolfgang Weich¹  Theodor Kudlich¹  Dorothee Rogoll¹  Lars Mayer²  Judit Pongracz³ 

[1] Department of Internal Medicine II, Gastroenterology, University Hospital Würzburg, 97080 Würzburg, Germany;Department of Nuclear Medicine, University Hospital Würzburg, 97080 Würzburg, Germany;Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, University of Pecs, 7630 Pecs, Hungary;

关键词: neuroendocrine tumor;    NET;    Wnt;    β-catenin;    CXCR4;    [⁶⁸Ga] Pentixafor;   

DOI  :  10.3390/diagnostics11020367

来源: DOAJ

【 摘 要 】

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 [⁶⁸Ga] 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 [⁶⁸Ga] 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.

【 授权许可】

Unknown