C-reactive protein inhibits expression of N-cadherin and ZEB-1 in murine colon adenocarcinoma

Tumour Biol. 2015 Sep;36(9):7035-43. doi: 10.1007/s13277-015-3414-2. Epub 2015 Apr 13.

Abstract

Epithelial-to-mesenchymal transition (EMT) is thought to play a key role in cancer cell invasion and metastasis. We previously demonstrated that cancer cell migration is inhibited by C-reactive protein (CRP), which is widely used as a biomarker of inflammation, though its functions are not fully understood. In the present study, we evaluated the effect of CRP on cancer cell migration and expression of mesenchymal and epithelial markers of EMT and of related transcription factors. MCA-38 murine colon adenocarcinoma cells were subcutaneously inoculated into the backs of C57BL/6 mice, which also received 1 μg of recombinant mouse CRP or vehicle (phosphate-buffered saline) subcutaneously every 3 days for 4 weeks. Thereafter, the mice were sacrificed for evaluation using quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry. There was no statistical difference in tumor size between the control and CRP groups, but CRP dose-dependently inhibited MCA-38 cell migration. PCR analysis confirmed that CRP suppresses expression of N-cadherin (p < 0.01), a mesenchymal marker of EMT, and ZEB-1, an EMT-related transcription factor (p < 0.01). These findings suggest that CRP inhibits EMT in a MCA-38 tumor-bearing mouse model. CRP may thus be a potentially useful tool for preventing cancer progression through suppression of EMT.

Keywords: C-reactive protein; E-cadherin; N-cadherin; ZEB-1.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Animals
  • C-Reactive Protein / administration & dosage*
  • C-Reactive Protein / genetics
  • Cadherins / biosynthesis*
  • Cadherins / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / biosynthesis*
  • Homeodomain Proteins / genetics
  • Humans
  • Kruppel-Like Transcription Factors / biosynthesis*
  • Kruppel-Like Transcription Factors / genetics
  • Mice
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / genetics
  • Zinc Finger E-box-Binding Homeobox 1

Substances

  • Cadherins
  • Homeodomain Proteins
  • Kruppel-Like Transcription Factors
  • Recombinant Proteins
  • ZEB1 protein, mouse
  • Zinc Finger E-box-Binding Homeobox 1
  • C-Reactive Protein