Cervical Cancer Cell Line Secretome Highlights the Roles of Transforming Growth Factor-Beta-Induced Protein ig-h3, Peroxiredoxin-2, and NRF2 on Cervical Carcinogenesis

Biomed Res Int. 2017:2017:4180703. doi: 10.1155/2017/4180703. Epub 2017 Feb 2.

Abstract

Cancer cells acquire unique secretome compositions that contribute to tumor development and metastasis. The aim of our study was to elucidate the biological processes involved in cervical cancer, by performing a proteomic analysis of the secretome from the following informative cervical cell lines: SiHa (HPV16+), HeLa (HPV18+), C33A (HPV-), and HCK1T (normal). Proteins were analyzed by 2D gel electrophoresis coupled to MALDI-TOF-MS. Enrichment of secreted proteins with characteristic profiles for each cell line was followed by the identification of differentially expressed proteins. Particularly, transforming growth factor-beta-induced protein ig-h3 (Beta ig-h3) and peroxiredoxin-2 (PRDX2) overexpression in the secretome of cancer cell lines was detected and confirmed by Western blot. Bioinformatics analysis identified the transcription factor NRF2 as a regulator of differentially expressed proteins in the cervical cancer secretome. NRF2 levels were measured by both Western blot and Multiple Reaction Monitoring (MRM) in the total cell extract of the four cell lines. NRF2 was upregulated in SiHa and C33A compared to HCK1T. In conclusion, the secreted proteins identified in cervical cancer cell lines indicate that aberrant NRF2-mediated oxidative stress response (OSR) is a prominent feature of cervical carcinogenesis.

MeSH terms

  • Algorithms
  • Carcinogenesis
  • Cell Line, Tumor
  • Computational Biology
  • Electrophoresis, Gel, Two-Dimensional
  • Extracellular Matrix Proteins / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • HeLa Cells
  • Human papillomavirus 16
  • Humans
  • NF-E2-Related Factor 2 / metabolism*
  • Papillomavirus Infections / complications
  • Peptides / chemistry
  • Peroxiredoxins / metabolism*
  • Proteomics
  • Signal Transduction
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Tandem Mass Spectrometry
  • Transforming Growth Factor beta / metabolism*
  • Uterine Cervical Neoplasms / metabolism*

Substances

  • Extracellular Matrix Proteins
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Peptides
  • Transforming Growth Factor beta
  • betaIG-H3 protein
  • PRDX2 protein, human
  • Peroxiredoxins