CD73 is associated with poor prognosis in HNSCC

Oncotarget. 2016 Sep 20;7(38):61690-61702. doi: 10.18632/oncotarget.11435.

Abstract

CD73 is a cell surface immunosuppressive enzyme involved in tumor progression and metastasis. While patients whose cancer cells express elevated CD73 are typically associated with an unfavorable outcome, the clinical impact of CD73 expression in patients with Head and neck squamous cell carcinoma (HNSCC) remains unclear. In the present study, we investigated the prognostic significance of CD73 in HNSCC using gene and protein expression analyses. Our results demonstrate that high levels of CD73 are significantly associated with reduced overall survival in patients with HNSCC. We also investigated the functional role of CD73 in vitro and demonstrated that CD73 promotes HNSCC migration and invasion through adenosine A3R stimulation and the activation of EGF/EGFR signaling. Moreover, in vivo xenograft studies demonstrated that CD73 promotes tumorigenesis. In conclusion, our study highlights a role for CD73 as a poor prognostic marker of patient survival and also as a candidate therapeutic target in HNSCCs.

Keywords: CD73; EGFR; EMT; adenosine receptor; head and neck squamous cell carcinoma.

MeSH terms

  • 5'-Nucleotidase / metabolism*
  • Animals
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • ErbB Receptors / metabolism
  • GPI-Linked Proteins / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Head and Neck Neoplasms / diagnosis*
  • Head and Neck Neoplasms / metabolism*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Lymphatic Metastasis
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Prognosis
  • Proportional Hazards Models
  • Receptor, Adenosine A3 / metabolism
  • Retrospective Studies
  • Signal Transduction
  • Squamous Cell Carcinoma of Head and Neck
  • Treatment Outcome
  • Up-Regulation

Substances

  • GPI-Linked Proteins
  • Immunosuppressive Agents
  • Receptor, Adenosine A3
  • ErbB Receptors
  • 5'-Nucleotidase
  • NT5E protein, human