Changes in gene expression by SNAI2 knockdown in the spheroid derived from human pancreatic cancer

The prognosis of pancreatic cancer is still poor due to resistance to conventional therapies, and cancer stem cells (CSCs) targeted therapy is expected to be a promising therapy. Although epithelial mesenchymal transition-inducing transcription factors (EMT-TF) are known to impart the CSCs properties to some of solid tumors, it has not been clearly reported in pancreatic cancer yet. Zinc finger protein SNAI2, a member of the Snail superfamily of EMT-TF, is frequently overexpressed in pancreatic cancer cells and the poor prognosis has been reported in cases with high SNAI2 expression. we found the suppression of SNAI2 expression using RNA interference decreased the tumorigenicity in the tumor spheroid (Sph) derived from surgically resected pancreatic cancer tissues. Also, it increased the sensitivities to Gemcitabine treatment and reduced the expression of CD44, one of the pancreatic CSCs markers. Furthemore, microarray analysis suggests that the mechanism is mediated by insulin-like growth factor binding protein 2 (IGFBP2). These results indicate that SNAI2 may be a critical factor for the CSCs properties and indispensable for the homeostasis of pancreatic CSCs. To elucidate whether SNAI2 involves in the properties of cancer stem cells, SNAI2 knockdown stable clones were generated by transduction of short hairpin RNA into the spheroid derived from human pancreatic cancer using lentiviral vector and analyzed in comparison with control vector.