The extracellular domain of E cadherin linked to invasiveness in colorectal cancer: a new resistance and relapses monitoring serum-bio marker?

J Cancer Res Clin Oncol. 2017 Jul;143(7):1177-1190. doi: 10.1007/s00432-017-2382-x. Epub 2017 Mar 13.

Abstract

Purpose: Multiple studies have attempted to demonstrate the interest of the cell adhesion marker, E cadherin, as a diagnostic and prognosis marker in colorectal cancer (CRC). However, it was considered non specific.

Materials and methods: Studies were carried out with CRC cell lines and patients' cohort operated for CRC. The expression of E cadherin was studied after 5 fluorouracil (5FU) treatment and correlated to CRC relapse, chemo-resistance and survival.

Results: In CRC cell lines derived from high tumor stages, extracellular domain of E cadherin expression decreased after 5FU treatment whereas it increased in supernatants. Interestingly, only specific cleaved forms at 55 kDa of E cadherin were detected in supernatants. In CRC surgical patients, more importantly concerning extracellular E cadherin domain, a decreased expression was observed in tissues in function of CRC stages whereas an increased expression was found in sera. Moreover, there is an increasing trend of survival with weak serum E cadherin secretion, reinforcing the implication of this protein in CRC evolution.

Discussion: The extracellular domain can be defined as a 5FU resistance marker and allow CRC monitoring.

Keywords: Colorectal cancer; E cadherin; Extracellular domain; Serum.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / blood*
  • Blotting, Western
  • Cadherins / metabolism*
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / pathology*
  • Disease-Free Survival
  • Drug Resistance, Neoplasm / physiology
  • Female
  • Fluorouracil / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / pathology*
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / pathology
  • Protein Domains

Substances

  • Antigens, CD
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • CDH1 protein, human
  • Cadherins
  • Fluorouracil