PMID- 27117272 OWN - NLM STAT- MEDLINE DCOM- 20161020 LR - 20190221 IS - 1916-0216 (Electronic) IS - 1916-0208 (Print) IS - 1916-0208 (Linking) VI - 45 DP - 2016 Apr 26 TI - In vivo Wnt pathway inhibition of human squamous cell carcinoma growth and metastasis in the chick chorioallantoic model. PG - 26 LID - 10.1186/s40463-016-0140-8 [doi] LID - 26 AB - BACKGROUND: Head 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. METHODS: We 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. RESULTS: UM-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. CONCLUSIONS: Our 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. FAU - Rudy, Shannon F AU - Rudy SF AD - Department of Otolaryngology/Head Neck Surgery, University of Michigan School of Medicine, Ann Arbor, MI, 48109-5616, USA. AD - Department of Otolaryngology/Head Neck Surgery, Stanford University, Stanford, CA, 94305, USA. FAU - Brenner, J Chad AU - Brenner JC AD - Department of Otolaryngology/Head Neck Surgery, University of Michigan School of Medicine, Ann Arbor, MI, 48109-5616, USA. AD - Comprehensive Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, 48109-5616, USA. FAU - Harris, Jennifer L AU - Harris JL AD - Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA, 92121, USA. FAU - Liu, Jun AU - Liu J AD - Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA, 92121, USA. FAU - Che, Jianwei AU - Che J AD - Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA, 92121, USA. FAU - Scott, Megan V AU - Scott MV AD - Comprehensive Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, 48109-5616, USA. AD - Wayne State University School of Medicine, Detroit, MI, 48201, USA. FAU - Owen, John Henry AU - Owen JH AD - Department of Otolaryngology/Head Neck Surgery, University of Michigan School of Medicine, Ann Arbor, MI, 48109-5616, USA. FAU - Komarck, Christine M AU - Komarck CM AD - Department of Otolaryngology/Head Neck Surgery, University of Michigan School of Medicine, Ann Arbor, MI, 48109-5616, USA. FAU - Graham, Martin P AU - Graham MP AD - Department of Otolaryngology/Head Neck Surgery, University of Michigan School of Medicine, Ann Arbor, MI, 48109-5616, USA. FAU - Bellile, Emily L AU - Bellile EL AD - Cancer Center Biostatistics Core, University of Michigan School of Medicine, Ann Arbor, MI, 48109-5616, USA. FAU - Bradford, Carol R AU - Bradford CR AD - Department of Otolaryngology/Head Neck Surgery, University of Michigan School of Medicine, Ann Arbor, MI, 48109-5616, USA. AD - Comprehensive Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, 48109-5616, USA. FAU - Prince, Mark E P AU - Prince ME AD - Department of Otolaryngology/Head Neck Surgery, University of Michigan School of Medicine, Ann Arbor, MI, 48109-5616, USA. AD - Comprehensive Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, 48109-5616, USA. FAU - Carey, Thomas E AU - Carey TE AD - Department of Otolaryngology/Head Neck Surgery, University of Michigan School of Medicine, Ann Arbor, MI, 48109-5616, USA. careyte@med.umich.edu. AD - Comprehensive Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, 48109-5616, USA. careyte@med.umich.edu. LA - eng GR - P50 CA097248/CA/NCI NIH HHS/United States GR - R01 DE019126/DE/NIDCR NIH HHS/United States GR - U01 DE025184/DE/NIDCR NIH HHS/United States GR - T32 DC05356/DC/NIDCD NIH HHS/United States GR - P50 CA 097248/CA/NCI NIH HHS/United States GR - P30 DC005188/DC/NIDCD NIH HHS/United States GR - T32 DC005356/DC/NIDCD NIH HHS/United States GR - P30 DC05188/DC/NIDCD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20160426 PL - England TA - J Otolaryngol Head Neck Surg JT - Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale JID - 101479544 RN - 0 (Receptor, Notch1) RN - 0 (WNT9A protein, human) RN - 0 (Wnt Proteins) RN - 9007-49-2 (DNA) SB - IM MH - Animals MH - Carcinoma, Squamous Cell/*genetics/metabolism/secondary MH - Cell Line, Tumor MH - Chick Embryo MH - Chorioallantoic Membrane/*metabolism/pathology MH - DNA/*genetics MH - DNA Mutational Analysis MH - Head and Neck Neoplasms/*genetics/metabolism/secondary MH - Humans MH - Mice MH - *Mutation MH - Neoplasm Metastasis MH - *Neoplasms, Experimental MH - Polymerase Chain Reaction MH - Receptor, Notch1/*genetics/metabolism MH - Squamous Cell Carcinoma of Head and Neck MH - Wnt Proteins/*genetics/metabolism MH - Wnt Signaling Pathway PMC - PMC4845503 OTO - NOTNLM OT - Cell lines OT - Chorioallantoic membrane OT - Human squamous cell carcinoma OT - In vivo cancer model OT - NOTCH1 mutation OT - UM-SCC OT - WNT pathway inhibition OT - WNT974 EDAT- 2016/04/28 06:00 MHDA- 2016/10/21 06:00 PMCR- 2016/04/26 CRDT- 2016/04/28 06:00 PHST- 2016/02/23 00:00 [received] PHST- 2016/04/19 00:00 [accepted] PHST- 2016/04/28 06:00 [entrez] PHST- 2016/04/28 06:00 [pubmed] PHST- 2016/10/21 06:00 [medline] PHST- 2016/04/26 00:00 [pmc-release] AID - 10.1186/s40463-016-0140-8 [pii] AID - 140 [pii] AID - 10.1186/s40463-016-0140-8 [doi] PST - epublish SO - J Otolaryngol Head Neck Surg. 2016 Apr 26;45:26. doi: 10.1186/s40463-016-0140-8.