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

Oncotarget. 2015 Apr 10;6(10):8313-22. doi: 10.18632/oncotarget.3228.

Abstract

CD133 has been implicated as a cancer stem cell (CSC) surface marker in several malignancies including pancreatic cancer. However, the functional role of this surface glycoprotein in the cancer stem cell remains elusive. In this study, we determined that CD133 overexpression induced "stemness" properties in MIA-PaCa2 cells along with increased tumorigenicity, tumor progression, and metastasis in vivo. Additionally, CD133 expression induced epithelial-mesenchymal transition (EMT) and increased in vitro invasion. EMT induction and increased invasiveness were mediated by NF-κB activation, as inhibition of NF-κB mitigated these effects. This study showed that CD133 expression contributes to pancreatic cancer "stemness," tumorigenicity, EMT induction, invasion, and metastasis.

Keywords: CD133; NF-kB; invasion; metastasis; pancreatic cancer.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • AC133 Antigen
  • Animals
  • Antigens, CD / biosynthesis*
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition / physiology*
  • Female
  • Glycoproteins / biosynthesis*
  • Heterografts
  • Humans
  • Mice
  • Mice, Nude
  • NF-kappa B / metabolism
  • Neoplasm Metastasis
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology*
  • Peptides
  • Signal Transduction

Substances

  • AC133 Antigen
  • Antigens, CD
  • Glycoproteins
  • NF-kappa B
  • PROM1 protein, human
  • Peptides
  • Prom1 protein, mouse