Evidence for epithelial-mesenchymal transition in cancer stem-like cells derived from carcinoma cell lines of the cervix uteri

Int J Clin Exp Pathol. 2015 Jan 1;8(1):847-55. eCollection 2015.

Abstract

The cancer stem cell (CSC) paradigm is one possible way to understand the genesis of cancer, and cervical cancer in particular. We quantified and enriched ALDH1(+) cells within cervical cancer cell lines and subsequently characterized their phenotypical and functional properties like invasion capacity and epithelial-mesenchymal transition (EMT). ALDH1 expression in spheroid-derived cells (SDC) and the parental monolayer-derived cell (MDC) line was compared by flow-cytometry. Invasion capability was evaluated by Matrigel assay and expression of EMT-related genes Twist 1, Twist 2, Snail 1, Snail 2, Vimentin and E-cadherin by real-time PCR. ALDH1 expression was significantly higher in SDC. ALDH1(+) cells showed increased colony-formation. SDC expressed lower levels of E-cadherin and elevated levels of Twist 1, Twist 2, Snail 1, Snail 2 and Vimentin compared to MDC. Cervical cancer cell lines harbor potential CSC, characterized by ALDH1 expression as well as properties like invasiveness, colony-forming ability, and EMT. CSC can be enriched by anchorage-independent culture techniques, which may be important for the investigation of their contribution to therapy resistance, tumor recurrence and metastasis.

Keywords: ALDH1; Cervical cancer; EMT; cancer stem cell; spheroid derived cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Dehydrogenase 1 Family
  • Carcinoma / pathology*
  • Cell Culture Techniques / methods*
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cervix Uteri
  • Epithelial-Mesenchymal Transition / physiology*
  • Female
  • Flow Cytometry
  • Humans
  • Isoenzymes / biosynthesis
  • Neoplasm Invasiveness / pathology
  • Neoplastic Stem Cells / pathology*
  • Real-Time Polymerase Chain Reaction
  • Retinal Dehydrogenase / biosynthesis
  • Uterine Cervical Neoplasms / pathology*

Substances

  • Isoenzymes
  • Aldehyde Dehydrogenase 1 Family
  • ALDH1A1 protein, human
  • Retinal Dehydrogenase