Association of eIF4E and SPARC Expression with Lymphangiogenesis and Lymph Node Metastasis in Hypopharyngeal Cancer

Anticancer Res. 2018 Feb;38(2):699-706. doi: 10.21873/anticanres.12275.

Abstract

Background/aim: Head and neck squamous cell carcinomas (HNSCC) are characterized by aggressiveness, early recurrence and lymph node metastasis. Therefore, there is an urgent need to identify new biomarkers and drug targets.

Materials and methods: Neck dissection specimens from 11 patients diagnosed with hypopharyngeal cancer were analyzed for their lymphatic vessel density (LVD) by lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) immunostaining, expression of eukaryotic initiation factor 4E (eIF4E) and levels of secreted protein acidic and rich in cysteine (SPARC) using immunoblot analysis.

Results: Compared to lymph node biopsies of healthy controIs, LVD was significantly increased in metastatic lymph nodes as well as in advanced primary tumors. Overexpression of eIF4E and SPARC was demonstrated in all hypopharyngeal cancer specimens. Notably, we observed that increased LVD significantly correlated with the expression of eIF4E as well as SPARC levels.

Conclusion: eIF4E- and SPARC-associated signaling pathways may be associated with lymphangiogenesis and could be exploited to counteract the spread of hypopharyngeal cancer cells.

Keywords: Lymphangiogenesis; SPARC; eIF4E; hypopharyngeal cancer; metastasis.

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Female
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / pathology
  • Humans
  • Hypopharyngeal Neoplasms / metabolism*
  • Hypopharyngeal Neoplasms / pathology*
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Lymphangiogenesis / physiology*
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Nucleocytoplasmic Transport Proteins / metabolism*
  • Osteonectin / metabolism*
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • Biomarkers, Tumor
  • EIF4ENIF1 protein, human
  • Nucleocytoplasmic Transport Proteins
  • Osteonectin
  • SPARC protein, human