HSP-enriched properties of extracellular vesicles involve survival of metastatic oral cancer cells

J Cell Biochem. 2018 Sep;119(9):7350-7362. doi: 10.1002/jcb.27039. Epub 2018 May 16.

Abstract

Cancer cells often secrete extracellular vesicles (EVs) that carry heat shock proteins (HSPs) with roles in tumor progression. Oral squamous cell carcinoma (OSCC) belongs to head and neck cancers (HNC) whose lymph-node-metastases often lead to poor prognosis. We have examined the EV proteome of OSCC cells and found abundant secretion of HSP90-enriched EVs in lymph-node-metastatic OSCC cells. Double knockdown of HSP90α and HSP90β, using small interfering RNA significantly reduced the survival of the metastatic OSCC cells, although single knockdown of each HSP90 was ineffective. Elevated expression of these HSP90 family members was found to correlate with poor prognosis of HNC cases. Thus, elevated HSP90 levels in secreted vesicles are potential prognostic biomarkers and therapeutic targets in metastatic OSCC.

Keywords: EV proteomics; exosome; extracellular vesicle; heat shock proteins; lymph-node-metastatic oral cancer; molecular chaperone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Cell Survival
  • Epithelial Cell Adhesion Molecule / metabolism
  • Extracellular Vesicles / metabolism*
  • Gene Expression
  • Gene Knockdown Techniques
  • HSP90 Heat-Shock Proteins / genetics*
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis / pathology*
  • Mouth Neoplasms / pathology*
  • Proteome / metabolism
  • RNA, Small Interfering / genetics

Substances

  • Biomarkers, Tumor
  • Epithelial Cell Adhesion Molecule
  • HSP90 Heat-Shock Proteins
  • HSP90AA2P protein, human
  • HSP90AB1 protein, human
  • Proteome
  • RNA, Small Interfering
  • TRAP1 protein, human