Abstract A24: CD133 initiates tumors, induces epithelial-mesenchymal transition, and increases metastasis in pancreatic cancer

CD133 has been implicated as a cancer stem cell (CSC) surface marker in several malignancies including pancreatic cancer, however, the functional role in the cancer stem cell remains elusive. In this study, we overexpressed CD133 CSC marker in a cell line with minimal endogenous CD133 in order to determine its functional role within a cancer context. We determined that CD133 expression led to increased tumorigenicity down to 10 cells. Progression of tumors derived from cells overexpressing CD133 increased in volume quicker than controls. Additionally, the number of lesions and sites of metastasis were increased in the orthotopic tumors derived from CD133 overexpressing cells. In vitro, CD133 expression induced epithelial-mesenchymal transition (EMT). Mesenchymal marker genes such as SNAI1, ZEB1, CDH2, and VIM increased upon CD133 overexpression and led to increased in vitro invasion by Boyden chamber invasion assay. Furthermore, our results indicate EMT induction and increased invasiveness were mediated by increased NF-κB activation upon CD133 overexpression, as inhibition of NF-κB mitigated these effects. In conclusion, this study demonstrated a functional role of CD133 in pancreatic cancer: its expression increases tumorigenicity; induces EMT; and increases invasion and metastasis. Citation Format: Alice Nomura, Sulagna Banerjee, Veena Sangwan, Rohit Chugh, Vikas Dudeja, Selwyn M. Vickers, Ashok K. Saluja. CD133 initiates tumors, induces epithelial-mesenchymal transition, and increases metastasis in pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A24.