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Stem Cells International
Volume 2016, Article ID 1894782, 10 pages
http://dx.doi.org/10.1155/2016/1894782
Research Article

Cancer Stem Cell Signaling during Repopulation in Head and Neck Cancer

1Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI 48703, USA
2Beaumont BioBank, William Beaumont Hospital, Royal Oak, MI 48703, USA
3Department of Human Oncology, University of Wisconsin Carbone Cancer Center, Madison, WI 53792, USA
4Department of Otolaryngology, William Beaumont Hospital, Royal Oak, MI 48703, USA
5Department of Radiation Oncology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA

Received 8 July 2015; Revised 7 October 2015; Accepted 15 November 2015

Academic Editor: Ahmad Waseem

Copyright © 2016 George D. Wilson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The aim of the study was to investigate cancer stem signaling during the repopulation response of a head and neck squamous cell cancer (HNSCC) xenograft after radiation treatment. Xenografts were generated from low passage HNSCC cells and were treated with either sham radiation or 15 Gy in one fraction. At different time points, days 0, 3, and 10 for controls and days 4, 7, 12, and 21, after irradiation, 3 tumors per group were harvested for global gene expression, pathway analysis, and immunohistochemical evaluation. 316 genes were identified that were associated with a series of stem cell-related genes and were differentially expressed ( and 1.5-fold) at a minimum of one time point in UT-SCC-14 xenografts after radiation. The largest network of genes that showed significant changes after irradiation was associated with CD44, NOTCH1, and MET. c-MET and ALDH1A3 staining correlated with the changes in gene expression. A clear pattern emerged that was consistent with the growth inhibition data in that genes associated with stem cell pathways were most active at day 7 and day 12 after irradiation. The MET/CD44 axis seemed to be an important component of the repopulation response.