Cancer Stem Cell Signaling during Repopulation in Head and Neck Cancer

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 (p ≤ 0.01 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.

Combined CD44, c‐MET, and EGFR expression in p16‐positive and p16‐negative head and neck squamous cell carcinomas

“…In HNSCC, the CD44/c‐MET signaling pathway is involved in tumor progression and has been shown to promote self‐renewal and differentiation in the vitro and in vivo setting . In addition, both CD44 and c‐MET signaling networks have also been shown to be differentially expressed during repopulation after radiation in a HNSCC xenograft model .…”

Tyrosine Kinase c-MET as Therapeutic Target for Radiosensitization of Head and Neck Squamous Cell Carcinomas

“…c-MET has been shown to be essential to maintain the subpopulation of cancer stem cells (CSCs) within tumors [ 31 , 32 ]. CSCs are characterized by infinite self-renewal, cellular plasticity, high migratory capacity and therapy resistance.…”

Hyaluronan-mediated ferric oxide nanoparticles causes apoptosis of CD44 expressing head and neck squamous cell carcinoma cells

“…We have preliminary data that intravenous injection of HA-DESPIONS into nude mice bearing UT-SCC-14 xenografts can be detected in a 3.0 Tesla benchtop MRI and that changes in MRI signal caused by radiation treatment correlate with observed changes in CD44 expression measured by immunohistochemistry and gene expression. 30 In addition we are exploring an RF pulse sequence technique to enable activation of hyperthermia of HA-DESPIONS in a clinical MRI. 31…”