Effect of serpinE1 overexpression on the primary tumor and lymph node, and lung metastases in head and neck squamous cell carcinoma

Head Neck. 2019 Feb;41(2):429-439. doi: 10.1002/hed.25437. Epub 2018 Dec 12.

Abstract

Background: Serpin Family E Member 1 (SerpinE1) overexpression associates with poor clinical outcome in head and neck squamous cell carcinoma (HNSCC) patients. This study analyzed the role of serpinE1 in HNSCC dissemination.

Methods: We studied the phenotypic characteristics and dissemination of HNSCC cells overexpressing serpinE1 using an orthotopic model and the association between serpinE1 overexpression and clinicopathological variables in patients included in The Cancer Genome Atlas database.

Results: SerpinE1 overexpression increased proliferation, tumor budding, and the stromal component, while inhibiting apoptosis in primary tumors. It also enhanced the affectation and metastatic growth in lymph nodes, and the dispersion and growth of metastatic foci in the lung. High serpinE1 expression was associated with larger tumor size, undifferentiated tumors, lymph node metastasis, extracapsular spread, and the presence of perineural and angiolymphatic invasion.

Conclusion: SerpinE1 overexpression promotes tumor aggressiveness and metastatic dissemination to lymph nodes and lung consistently with its association with poor outcome in HNSCC patients.

Keywords: HNSCC; dissemination; orthotopic mouse model; serpinE1; tumor aggressiveness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cohort Studies
  • Databases, Factual
  • Disease Models, Animal
  • Female
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / pathology
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / secondary
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Male
  • Mice
  • Mice, Inbred NOD
  • Plasminogen Activator Inhibitor 1 / genetics*
  • Plasminogen Activator Inhibitor 1 / metabolism
  • RNA, Messenger / metabolism
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / metabolism*
  • Squamous Cell Carcinoma of Head and Neck / secondary

Substances

  • Plasminogen Activator Inhibitor 1
  • RNA, Messenger