Wnt/β-catenin signaling regulates CXCR4 expression and [\(^{68}\)Ga] Pentixafor internalization in neuroendocrine tumor cells
Please always quote using this URN: urn:nbn:de:bvb:20-opus-228914
- 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,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.…
Author: | Alexander Weich, Dorothee Rogoll, Sophia Gawlas, Lars Mayer, Wolfgang Weich, Judit Pongracz, Theodor Kudlich, Alexander Meining, Michael Scheurlen |
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URN: | urn:nbn:de:bvb:20-opus-228914 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Klinik und Poliklinik für Nuklearmedizin |
Medizinische Fakultät / Medizinische Klinik und Poliklinik II | |
Language: | English |
Parent Title (English): | Diagnostics |
ISSN: | 2075-4418 |
Year of Completion: | 2021 |
Volume: | 11 |
Issue: | 2 |
Article Number: | 367 |
Source: | Diagnostics (2021) 11:2, 367. https://doi.org/10.3390/diagnostics11020367 |
DOI: | https://doi.org/10.3390/diagnostics11020367 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | BON-1; CXCR4; MS-18; NET; QGP-1; Wnt; [\(^{68}\)Ga] Pentixafor; neuroendocrine tumor; β-catenin |
Release Date: | 2022/08/29 |
Date of first Publication: | 2021/02/22 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |