期刊
DIAGNOSTICS
卷 11, 期 2, 页码 -出版社
MDPI
DOI: 10.3390/diagnostics11020367
关键词
neuroendocrine tumor; NET; Wnt; beta-catenin; CXCR4; [68Ga] Pentixafor; BON-1; QGP-1; MS-18
资金
- Novartis Pharma GmbH
- YING Grant
Loss of Somatostatin Receptor 2 (SSTR2) expression and rising CXC Chemokine Receptor Type 4 (CXCR4) expression are associated with dedifferentiation in neuroendocrine tumors (NET). Activation of Wnt/beta-catenin signaling may promote a more aggressive phenotype in NET. Modulation of the Wnt pathway influences CXCR4 expression and function in NET cell lines, suggesting it may enhance the efficacy of CXCR4-directed therapies or inhibit CXCR4-dependent proliferative signaling.
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/beta-catenin signaling may promote a more aggressive phenotype in NET. We hypothesized an interaction of the Wnt/beta-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 [Ga-68] 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 [Ga-68] 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.
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