Abstract
BackgroundHead and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with poor overall survival. New therapeutic strategies that target specific molecular lesions driving advanced disease are needed. Herein we demonstrate the utility of the chicken chorioallantoic membrane (CAM) assay for in vivo human HNSCC tumor growth and metastasis and the tumor suppressive effects of a new chemotherapeutic agent.MethodsWe tested anti-metastatic effects of a WNT pathway inhibitor, WNT974 (also known as LGK974), which targets porcupine (PORCN) the palmityl-transferase that is essential for secretion of Wnt proteins. CAM assays were performed with 8 HNSCC cell lines: UM-SCC-1, UM-SCC-10A, UM-SCC-10B, UM-SCC-11A, UM-SCC-14A UM-SCC-17A, UM-SCC-17B, UM-SCC-25, and UM-SCC-34.ResultsUM-SCC-1 (University of Michigan Squamous Cell Carcinoma cell line) CAM xenografts contain CD44+ and ALDH+ cancer stem cell (CSC) proportions similar to UM-SCC-1 mouse xenografts supporting the applicability of the CAM assay for study of CSCs. Inhibition of WNT signaling by the PORCN inhibitor WNT974 reduced metastatic spread of UM-SCC cells, especially in UM-SCCs with Notch1 deficiency.ConclusionsOur data demonstrate decreased tumor growth and metastases in tumors from cell lines that showed in vitro responses to WNT974, providing evidence that this agent may have a role in future HNSCC therapy.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with poor overall survival
UM-SCC cell lines grow and metastasize in chorioallantoic membrane (CAM) assays Five chick embryos were implanted with cancer cells for each of the eight UMSCC cell lines tested in this study
The number of viable embryos examined for tumor growth is given following the cell line: UM-SCC-1: 5, UM-SCC-10A: 3, UM-SCC-10B: 4, UM-SCC-11A: 5, UM-SCC-17A: 3, UM-SCC-17B: 5, UM-SCC-25: 5, and UM-SCC-34: 4 embryos
Summary
Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with poor overall survival. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common form of cancer worldwide [1]. The Wnt signaling pathway is an appealing target, as this developmental pathway has been implicated in a large number of human cancers, with recent evidence for an oncogenic role in HNSCC [6]. Once activated by Wnt, the Frizzled receptors inhibit the destruction complex through incompletely understood mechanisms. Together, this leads to an accumulation of β-catenin protein, which can translocate to the nucleus to form a complex with LEF/TCF proteins to regulate transcription of proliferation associated genes
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