Further investigation identified a subpopulation of cells that are characterised by high aldehyde dehydrogenase (ALDH) activity, enhanced radioresistance and decreased expression of miR-17-5p.
OE33 R cells demonstrate enhanced tumorigenicity in vivo
A. OE33 P and OE33 R cells were implanted subcutaneously into NOD SCID mice (n=3). OE33 R cells demonstrated significantly enhanced tumorigenesis when compared to OE33 P cells. Data are presented as the mean ± SEM. Statistical analysis was performed using a two-tailed unpaired Student’s t-test,***p < 0.0001 B. Representative images of tumors extracted from OE33 P and OE33 R cells injected into NOD SCID mice.
In vitro, miR-17-5p was demonstrated to significantly sensitise radioresistant cells to X-ray radiation and promoted the repression of genes with miR-17-5p binding sites, such as C6orf120. In vivo, miR-17-5p was significantly decreased, whilst C6orf120 was significantly increased, in pre-treatment EAC tumour samples from patients who demonstrated a poor response to neoadjuvant CRT.
This study sheds novel insights into the role of CSCs in the resistance of EAC to CRT and highlights miR-17-5p as a potential biomarker of CRT sensitivity and novel therapeutic target in treatment resistant EAC.